Browsing by Author "Bhatti, Gurjit Kaur"

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Advances and challenges in thyroid cancer: The interplay of genetic modulators, targeted therapies, and AI-driven approaches
(Elsevier Inc., 2023-09-20T00:00:00) Bhattacharya, Srinjan; Mahato, Rahul Kumar; Singh, Satwinder; Bhatti, Gurjit Kaur; Mastana, Sarabjit Singh; Bhatti, Jasvinder Singh
Thyroid cancer continues to exhibit a rising incidence globally, predominantly affecting women. Despite stable mortality rates, the unique characteristics of thyroid carcinoma warrant a distinct approach. Differentiated thyroid cancer, comprising most cases, is effectively managed through standard treatments such as thyroidectomy and radioiodine therapy. However, rarer variants, including anaplastic thyroid carcinoma, necessitate specialized interventions, often employing targeted therapies. Although these drugs focus on symptom management, they are not curative. This review delves into the fundamental modulators of thyroid cancers, encompassing genetic, epigenetic, and non-coding RNA factors while exploring their intricate interplay and influence. Epigenetic modifications directly affect the expression of causal genes, while long non-coding RNAs impact the function and expression of micro-RNAs, culminating in tumorigenesis. Additionally, this article provides a concise overview of the advantages and disadvantages associated with pharmacological and non-pharmacological therapeutic interventions in thyroid cancer. Furthermore, with technological advancements, integrating modern software and computing into healthcare and medical practices has become increasingly prevalent. Artificial intelligence and machine learning techniques hold the potential to predict treatment outcomes, analyze data, and develop personalized therapeutic approaches catering to patient specificity. In thyroid cancer, cutting-edge machine learning and deep learning technologies analyze factors such as ultrasonography results for tumor textures and biopsy samples from fine needle aspirations, paving the way for a more accurate and effective therapeutic landscape in the near future. � 2023 The Author(s)
Advancing Cancer Immunotherapy: The Potential of mRNA Vaccines As a Promising Therapeutic Approach
(John Wiley and Sons Inc, 2023-10-04T00:00:00) Goyal, Falak; Chattopadhyay, Anandini; Navik, Umashanker; Jain, Aklank; Reddy, P. Hemachandra; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
mRNA vaccines have long been recognized for their ability to induce robust immune responses. The discovery that mRNA vaccines may also contribute to antitumor immunity has made them a promising therapeutic approach against cancer. Recent advances in understanding of immune system are precious in developing therapeutic strategies that target pathways involved in tumor survival and progression, leading to the most reliable therapeutic strategies in cancer treatment history. Among all traditional cancer treatments, cancer immunotherapies are less toxic and more effective, even in advanced or recurrent stages of cancer. Recent advancements in genomics and machine learning algorithms give new insight into vaccine development. mRNA vaccines are designed to interfere with stimulator of interferon genes (STING) and tumor-infiltrating lymphocytes pathways, activating more CD8+ T-cells involved in destroying tumor cells and inhibiting tumor growth. A stronger immune response can be achieved by incorporating immunological adjuvants alongside mRNA. Nonformulated or vehicle-based mRNA vaccines, when combined with adjuvants, efficiently express tumor antigens through antigen-presenting cells and stimulate both innate and adaptive immune responses. Codelivery with additional immunotherapeutic agents, such as checkpoint inhibitors, further enhances the efficacy of mRNA vaccines. This article focuses on the current clinical approaches and challenges to consider when developing mRNA-based vaccine technology for cancer treatment. � 2023 Wiley-VCH GmbH.
Dysregulated autophagy: A key player in the pathophysiology of type 2 diabetes and its complications
(Elsevier B.V., 2023-02-14T00:00:00) Sehrawat, Abhishek; Mishra, Jayapriya; Mastana, Sarabjit Singh; Navik, Umashanker; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Autophagy is essential in regulating the turnover of macromolecules via removing damaged organelles, misfolded proteins in various tissues, including liver, skeletal muscles, and adipose tissue to maintain the cellular homeostasis. In these tissues, a specific type of autophagy maintains the accumulation of lipid droplets which is directly related to obesity and the development of insulin resistance. It appears to play a protective role in a normal physiological environment by eliminating the invading pathogens, protein aggregates, and damaged organelles and generating energy and new building blocks by recycling the cellular components. Ageing is also a crucial modulator of autophagy process. During stress conditions involving nutrient deficiency, lipids excess, hypoxia etc., autophagy serves as a pro-survival mechanism by recycling the free amino acids to maintain the synthesis of proteins. The dysregulated autophagy has been found in several ageing associated diseases including type 2 diabetes (T2DM), cancer, and neurodegenerative disorders. So, targeting autophagy can be a promising therapeutic strategy against the progression to diabetes related complications. Our article provides a comprehensive outline of understanding of the autophagy process, including its types, mechanisms, regulation, and role in the pathophysiology of T2DM and related complications. We also explored the significance of autophagy in the homeostasis of ?-cells, insulin resistance (IR), clearance of protein aggregates such as islet amyloid polypeptide, and various insulin-sensitive tissues. This will further pave the way for developing novel therapeutic strategies for diabetes-related complications. � 2023 Elsevier B.V.
Emerging role of non?coding RNA in health and disease
(Springer, 2021-04-21T00:00:00) Bhatti, Gurjit Kaur; Khullar, Naina; Sidhu, Inderpal Singh; Navik, Uma Shanker; Reddy, Arubala P.; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and cure for every disease condition. With the advent and advancement in technology, the molecular arena at the microscopic level to study the mechanism, progression, and therapy is more rational and authentic pave than a macroscopic approach. Non-coding RNAs (ncRNAs) have now emerged as indispensable players in the diagnosis, development, and therapeutics of every abnormality concerning physiology, pathology, genetics, epigenetics, oncology, and developmental diseases. This is a comprehensive attempt to collate all the existing and proven strategies, techniques, mechanisms of genetic disorders including Silver Russell Syndrome, Fascio- scapula humeral muscular dystrophy, cardiovascular diseases (atherosclerosis, cardiac fibrosis, hypertension, etc.), neurodegenerative diseases (Spino-cerebral ataxia type 7, Spino-cerebral ataxia type 8, Spinal muscular atrophy, Opitz-Kaveggia syndrome, etc.) cancers (cervix, breast, lung cancer, etc.), and infectious diseases (viral) studied so far. This article encompasses discovery, biogenesis, classification, and evolutionary prospects of the existence of this junk RNA along with the integrated networks involving chromatin remodelling, dosage compensation, genome imprinting, splicing regulation, post-translational regulation and proteomics. In conclusion, all the major human diseases are discussed with a facilitated technology transfer, advancements, loopholes, and tentative future research prospects have also been proposed. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Gut microbiota dysbiosis and Huntington's disease: Exploring the gut-brain axis and novel microbiota-based interventions
(Elsevier Inc., 2023-06-24T00:00:00) Sharma, Garvita; Biswas, Shristi Saroj; Mishra, Jayapriya; Navik, Umashanker; Kandimalla, Ramesh; Reddy, P. Hemachandra; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
Huntington's disease (HD) is a complex progressive neurodegenerative disorder affected by genetic, environmental, and metabolic factors contributing to its pathogenesis. Gut dysbiosis is termed as the alterations of intestinal microbial profile. Emerging research has highlighted the pivotal role of gut dysbiosis in HD, focusing on the gut-brain axis as a novel research parameter in science. This review article provides a comprehensive overview of gut microbiota dysbiosis and its relationship with HD and its pathogenesis along with the future challenges and opportunities. The focuses on the essential mechanisms which link gut dysbiosis to HD pathophysiology including neuroinflammation, immune system dysregulation, altered metabolites composition, and neurotransmitter imbalances. We also explored the impacts of gut dysbiosis on HD onset, severity, and symptoms such as cognitive decline, motor dysfunction, and psychiatric symptoms. Furthermore, we highlight recent advances in therapeutics including microbiota-based therapeutic approaches, including dietary interventions, prebiotics, probiotics, fecal microbiota transplantation, and combination therapies with conventional HD treatments and their applications in managing HD. The future challenges are also highlighted as the heterogeneity of gut microbiota, interindividual variability, establishing causality between gut dysbiosis and HD, identifying optimal therapeutic targets and strategies, and ensuring the long-term safety and efficacy of microbiota-based interventions. This review provides a better understanding of the potential role of gut microbiota in HD pathogenesis and guides the development of novel therapeutic approaches. � 2023 Elsevier Inc.
Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies
(Baishideng Publishing Group Inc, 2023-04-12T00:00:00) Khullar, Naina; Bhatti, Jasvinder Singh; Singh, Satwinder; Thukral, Bhawana; Hemachandra Reddy, P.; Bhatti, Gurjit Kaur
As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors. It has also been reported that in some patients with COVID-19, therapeutic strategies, including repurposed drugs (mitifovir, lopinavir/ritonavir, tocilizumab, etc.) triggered liver injury and cholestatic toxicity. Several proven indicators support cytokine storm-induced hepatic damage. Because there are 1.5 billion patients with chronic liver disease worldwide, it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics. This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19. � The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Lifestyle modifications and nutrition in Alzheimer's disease
(Elsevier, 2023-06-16T00:00:00) Bhatti, Gurjit Kaur; Mishra, Jayapriya; Sehrawat, Abhishek; Sharma, Eva; Kanozia, Rubal; Navik, Umashanker; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Alzheimer's disease (AD) is a progressive chronic neurodegenerative disorder that is increasingly seen in developed and developing countries that subjugate older people. The exacerbation begins with the disease seen with the symptoms like deterioration of mental ability, memory, and cognitive deficits, which ultimately decline the physical activity also, and the severity of this disease causes the death of the patient. There is no proper medication and cure available to date, which can precisely prevent the condition efficiently. But it is essential to diagnose it before its destructive phase and consult for necessary treatments and procedures taken by the patient and the caregivers. Apart from clinical trials, the first and foremost thing is to focus on lifestyle; a way of living can have a more significant impact on a person's health. One can stay healthy for a longer time or fight against the disease by developing strategies like boosting immunity and staying physically fit enough, or else, one can successfully delay the appearance of disease with strong immunity and a healthier lifestyle. And the other promising fact is taking nutritious food, which is helpful to build a robust internal defense system against the diseased condition and lowering the risk of ailments. This chapter will focus on the pathophysiology of Alzheimer's disease, lifestyle modifications, and nutritional interventions in AD. � 2023 Elsevier Inc. All rights reserved.
Microbiome in Pulmonary Tuberculosis
(Springer Nature, 2022-03-25T00:00:00) Rakshit, Arnab; Verma, Aarti; Verma, Saloni; Bhatti, Gurjit Kaur; Khurana, Amit; Bhatti, Jasvinder Singh; Jawalekar, Snehal Sainath; Navik, Umashanker
Tuberculosis (TB) is among the global dominant fatal infection caused by a single organism, and it is still holding its position in spite of the golden age of the antibiotics. The recent studies are mostly focused on finding the prevention of TB rather than curing it because the antimycobacterial chemotherapy is failing constantly due to emerging multidrug resistance (MDR). Further, the intestinal microbiota is the central command for maintaining the homeostasis of the microbial profile of different organs. The change in the intestinal microbiota effects homeostasis by impacting the immune response to the microbial profile of various organs. Thus, it also affects the chance of contracting the infections. Here in this chapter, it is mostly focused on the reason behind the TB getting chance to infect the healthy lung tissue. It is also found that dysbiosis in gut microbiota, which directly affects the lung, plays a key role in giving TB a chance to hold its ground. It also highlights the new curative method which we can apply by correcting the gut microbial profile, which in turn corrects the lung microbial profile and rest of the function will done by body�s own immune system. It is thus found that proper restoration of the microbial profile enhances the immune response and could restore the homeostasis. � The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2022.
Mitochondrial miRNA as epigenomic signatures: Visualizing aging-associated heart diseases through a new lens
(Elsevier Ireland Ltd, 2023-02-11T00:00:00) Bhatti, Jasvinder Singh; Khullar, Naina; Vijayvergiya, Rajesh; Navik, Umashanker; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra
Aging bears many hard knocks, but heart disorders earn a particular allusion, being the most widespread. Cardiovascular diseases (CVDs) are becoming the biggest concern to mankind due to sundry health conditions directly or indirectly related to heart-linked abnormalities. Scientists know that mitochondria play a critical role in the pathophysiology of cardiac diseases. Both environment and genetics play an essential role in modulating and controlling mitochondrial functions. Even a minor abnormality may prove detrimental to heart function. Advanced age combined with an unhealthy lifestyle can cause most cardiomyocytes to be replaced by fibrotic tissue which upsets the conducting system and leads to arrhythmias. An aging heart encounters far more heart-associated comorbidities than a young heart. Many state-of-the-art technologies and procedures are already being used to prevent and treat heart attacks worldwide. However, it remains a mystery when this heart bomb would explode because it lacks an alarm. This calls for a novel and effective strategy for timely diagnosis and a sure-fire treatment. This review article provides a comprehensive overture of prospective potentials of mitochondrial miRNAs that predict complicated and interconnected pathways concerning heart ailments and signature compilations of relevant miRNAs as biomarkers to plot the role of miRNAs in epigenomics. This article suggests that analysis of DNA methylation patterns in age-associated heart diseases may determine age-impelled biomarkers of heart disease. � 2023 Elsevier B.V.
Modulating autophagy and mitophagy as a promising therapeutic approach in neurodegenerative disorders
(Elsevier Inc., 2022-11-04T00:00:00) Mishra, Jayapriya; Bhatti, Gurjit Kaur; Sehrawat, Abhishek; Singh, Charan; Singh, Arti; Reddy, Arubala P.; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
The high prevalence of neurodegenerative diseases has become a major public health challenge and is associated with a tremendous burden on individuals, society and federal governments worldwide. Protein misfolding and aggregation are the major pathological hallmarks of several neurodegenerative disorders. The cells have evolved several regulatory mechanisms to deal with aberrant protein folding, namely the classical ubiquitin pathway, where ubiquitination of protein aggregates marks their degradation via lysosome and the novel autophagy or mitophagy pathways. Autophagy is a catabolic process in eukaryotic cells that allows the lysosome to recycle the cell's own contents, such as organelles and proteins, known as autophagic cargo. Their most significant role is to keep cells alive in distressed situations. Mitophagy is also crucial for reducing abnormal protein aggregation and increasing organelle clearance and partly accounts for maintaining cellular homeostasis. Furthermore, substantial data indicate that any disruption in these homeostatic mechanisms leads to the emergence of several age-associated metabolic and neurodegenerative diseases. So, targeting autophagy and mitophagy might be a potential therapeutic strategy for a variety of health conditions. � 2022
Nanotheranostics revolutionizing neurodegenerative diseases: From precision diagnosis to targeted therapies
(Editions de Sante, 2023-10-16T00:00:00) Joshi, Riya; Missong, Hemi; Mishra, Jayapriya; Kaur, Satinder; Saini, Sumant; Kandimalla, Ramesh; Reddy, P. Hemachandra; Babu, Arockia; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
Neurodegenerative disorders pose a significant burden on global healthcare systems, and the development of effective therapeutics and diagnostics remains a critical challenge. Nanotheranostics, the integration of nanotechnology-based diagnostic and therapeutic modalities, has emerged as a promising strategy to address these challenges. This review article provides a comprehensive analysis of the latest advancements in nanotheranostics for the treatment and monitoring of neurological disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The application of targeted drug delivery systems, gene therapy, and non-invasive imaging techniques are explored in-depth, highlighting the potential of nanotheranostics to revolutionize the management of neurological disorders. The article delves into the design and synthesis of various nanocarriers, such as liposomes, dendrimers, and polymeric nanoparticles, which enable the targeted delivery of therapeutic agents across the blood-brain barrier. Gene therapy approaches, including CRISPR/Cas9 and RNA interference demonstrating the potential of nanotheranostics to enable precise genetic modifications in the treatment of neurological disorders. Additionally, non-invasive imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), are examined in the context of their integration with nanotheranostics for real-time monitoring of treatment efficacy and disease progression. The review also identifies current challenges and limitations in the field of nanotheranostics, such as toxicity, immunogenicity, and issues with large-scale production. Furthermore, it outlines future research directions and potential strategies to overcome these limitations, paving the way for the clinical translation of nanotheranostics as next-generation therapeutics in neurological disorders. � 2023
Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives
(Elsevier Inc., 2022-04-07T00:00:00) Bhatti, Jasvinder Singh; Sehrawat, Abhishek; Mishra, Jayapriya; Sidhu, Inderpal Singh; Navik, Umashanker; Khullar, Naina; Kumar, Shashank; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra
Type 2 diabetes (T2DM) is a persistent metabolic disorder rising rapidly worldwide. It is characterized by pancreatic insulin resistance and ?-cell dysfunction. Hyperglycemia induced reactive oxygen species (ROS) production and oxidative stress are correlated with the pathogenesis and progression of this metabolic disease. To counteract the harmful effects of ROS, endogenous antioxidants of the body or exogenous antioxidants neutralise it and maintain bodily homeostasis. Under hyperglycemic conditions, the imbalance between the cellular antioxidant system and ROS production results in oxidative stress, which subsequently results in the development of diabetes. These ROS are produced in the endoplasmic reticulum, phagocytic cells and peroxisomes, with the mitochondrial electron transport chain (ETC) playing a pivotal role. The exacerbated ROS production can directly cause structural and functional modifications in proteins, lipids and nucleic acids. It also modulates several intracellular signaling pathways that lead to insulin resistance and impairment of ?-cell function. In addition, the hyperglycemia-induced ROS production contributes to micro- and macro-vascular diabetic complications. Various in-vivo and in-vitro studies have demonstrated the anti-oxidative effects of natural products and their derived bioactive compounds. However, there is conflicting clinical evidence on the beneficial effects of these antioxidant therapies in diabetes prevention. This review article focused on the multifaceted role of oxidative stress caused by ROS overproduction in diabetes and related complications and possible antioxidative therapeutic strategies targeting ROS in this disease. � 2022 Elsevier Inc.
Progression of pre-rheumatoid arthritis to clinical disease of joints: Potential role of mesenchymal stem cells
(Elsevier Inc., 2023-03-28T00:00:00) Sardana, Yogesh; Bhatti, Gurjit Kaur; Singh, Charan; Sharma, Pushpender Kumar; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Rheumatoid arthritis (RA) related autoimmunity is developed at mucosal sites due to the interplay between genetic risk factors and environmental triggers. The pre-RA phase that leads to anti-citrullinated protein antibodies, rheumatoid factor, and other autoantibodies spread in the systemic circulation may not affect articular tissue for years until a mysterious second hit triggers the localization of RA-related autoimmunity in joints. Several players in the joint microenvironment mediate the synovial innate and adaptive immunological processes, eventually leading to clinical synovitis. There still exists a gap in the early phase of RA pathogenesis, i.e., the progression of diseases from the systemic circulation to joints. The lack of better understanding of these events results in the inability to answer questions about why only after a certain point of time the disease appears in joints and why in some cases, it simply remains latent and doesn't affect joints at all. In the current review, we focused on the immunomodulatory and regenerative role of mesenchymal stem cells and associated exosomes in RA pathology. We also highlighted the age-related dysregulations in activities of mesenchymal stem cells and how that might trigger homing of systemic autoimmunity to joints. � 2023 Elsevier Inc.
Protective role of natural products and bioactive compounds in multiple sclerosis
(Elsevier, 2023-06-16T00:00:00) Bhatti, Gurjit Kaur; Singh, Harsh Vikram; Sharma, Eva; Sehrawat, Abhishek; Mishra, Jayapriya; Navik, Umashanker; Hemachandra Reddy, P.; Bhatti, Jasvinder Singh
Multiple sclerosis (MS), a chronic multifactorial disease characterized by progressive demyelination and neurodegeneration, is rising rapidly in young adults. The pathology of the disease is not yet understood completely. However, neuroinflammation, oxidative stress, and hyperactive autoimmune response appear to play a prominent role in the pathogenesis of the disease. Several genetic, nongenetic, and environmental factors are also found associated with this autoimmune disorder. Although, it is still a matter of debate whether diet and lifestyle have an influence during the course of MS. Recent studies have highlighted several beneficial characteristics of natural bioactive compounds such as anti-inflammatory, antioxidative, immunomodulatory, and other neuroprotective effects, indicating their therapeutic potential to reduce the risk or ameliorate the progression of MS. Basically, these bioactive compounds are the chemicals found in minute amounts naturally in plants with peculiar health benefits. In this chapter, we have briefly described various natural bioactive compounds with neuroprotective effects against MS, including the polyphenols, vitamins supplementation, and natural products such as ginger, ashwagandha, and it seems that these compounds play a notable role in the treatment of MS. Further research is required to extend our understanding in developing more effective therapeutic strategies against the disease with lesser side effects. � 2023 Elsevier Inc. All rights reserved.
Stem cells in the treatment of Alzheimer's disease � Promises and pitfalls
(Elsevier B.V., 2023-04-06T00:00:00) Bhatti, Jasvinder Singh; Khullar, Naina; Mishra, Jayapriya; Kaur, Satinder; Sehrawat, Abhishek; Sharma, Eva; Bhatti, Gurjit Kaur; Selman, Ashley; Reddy, P. Hemachandra
Alzheimer's disease (AD) is the most widespread form of neurodegenerative disorder that causes memory loss and multiple cognitive issues. The underlying mechanisms of AD include the build-up of amyloid-? and phosphorylated tau, synaptic damage, elevated levels of microglia and astrocytes, abnormal microRNAs, mitochondrial dysfunction, hormonal imbalance, and age-related neuronal loss. However, the etiology of AD is complex and involves a multitude of environmental and genetic factors. Currently, available AD medications only alleviate symptoms and do not provide a permanent cure. Therefore, there is a need for therapies that can prevent or reverse cognitive decline, brain tissue loss, and neural instability. Stem cell therapy is a promising treatment for AD because stem cells possess the unique ability to differentiate into any type of cell and maintain their self-renewal. This article provides an overview of the pathophysiology of AD and existing pharmacological treatments. This review article focuses on the role of various types of stem cells in neuroregeneration, the potential challenges, and the future of stem cell-based therapies for AD, including nano delivery and gaps in stem cell technology. � 2023 Elsevier B.V.
Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in Parkinson's disease
(Elsevier Inc., 2023-08-02T00:00:00) Kaur, Satinder; Sehrawat, Abhishek; Mastana, Sarabjit Singh; Kandimalla, Ramesh; Sharma, Pushpender Kumar; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory. � 2023 Elsevier Inc.
Targeting dynamin-related protein-1 as a potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease
(Elsevier B.V., 2023-06-29T00:00:00) Bhatti, Jasvinder Singh; Kaur, Satinder; Mishra, Jayapriya; Dibbanti, Harikrishnareddy; Singh, Arti; Reddy, Arubala P.; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra
Alzheimer's disease (AD) is a neurodegenerative disease that manifests its pathology through synaptic damage, mitochondrial abnormalities, microRNA deregulation, hormonal imbalance, increased astrocytes & microglia, accumulation of amyloid ? (A?) and phosphorylated Tau in the brains of AD patients. Despite extensive research, the effective treatment of AD is still unknown. Tau hyperphosphorylation and mitochondrial abnormalities are involved in the loss of synapses, defective axonal transport and cognitive decline in patients with AD. Mitochondrial dysfunction is evidenced by enhanced mitochondrial fragmentation, impaired mitochondrial dynamics, mitochondrial biogenesis and defective mitophagy in AD. Hence, targeting mitochondrial proteins might be a promising therapeutic strategy in treating AD. Recently, dynamin-related protein 1 (Drp1), a mitochondrial fission protein, has gained attention due to its interactions with A? and hyperphosphorylated Tau, altering mitochondrial morphology, dynamics, and bioenergetics. These interactions affect ATP production in mitochondria. A reduction in Drp1 GTPase activity protects against neurodegeneration in AD models. This article provides a comprehensive overview of Drp1's involvement in oxidative damage, apoptosis, mitophagy, and axonal transport of mitochondria. We also highlighted the interaction of Drp1 with A? and Tau, which may contribute to AD progression. In conclusion, targeting Drp1 could be a potential therapeutic approach for preventing AD pathology. � 2023
Targeting Mitochondria as a Novel Disease-Modifying Therapeutic Strategy in Cancer
(Springer Singapore, 2022-09-28T00:00:00) Bhatti, Gurjit Kaur; Pahwa, Paras; Gupta, Anshika; Sidhu, Inderpal Singh; Navik, Uma Shanker; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Mitochondria are essential for the metabolism of energy, regulation of apoptosis, and cell signaling. Overproduction of reactive oxidation species (ROS) in mitochondria is one of the indications of cancer cells. Moreover, this boosts the proliferation of cancerous cells by causing genomic instability and altering gene expressions. Mitochondrial and nuclear DNA mutations caused by oxidative damage impair the mechanism of oxidative phosphorylation and can lead to more mitochondrial ROS output, genome instability, and cancer development. The classic approach to target mitochondria of cancerous cells with novel targeted therapeutics helps in targeting the mitochondrial apoptotic proteins and changing energy metabolism. A key benefit of selective drug delivery is that it reduces the drug�s toxicity and increases specificity. A better understanding of the mitochondrial role in tumor growth will help design more therapeutic agents with better selectivity. � Springer Nature Singapore Pte Ltd. 2022.
Targeting Mitochondria as a Novel Disease-Modifying Therapeutic Strategy in Cancer
(Springer Nature, 2022-01-31T00:00:00) Bhatti, Gurjit Kaur; Pahwa, Paras; Gupta, Anshika; Navik, Uma Shanker; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Mitochondria are important for the metabolism of energy, regulation of apoptosis and cell signaling. Overproduction of reactive oxidation species (ROS) in mitochondria is one of the indications of cancer cells; moreover, this boosts the proliferation of cancerous cells by causing genomic instability and altering gene expressions. Mitochondrial and nuclear DNA mutations, caused by oxidative damage which impairs the mechanism of oxidative phosphorylation, can lead to more mitochondrial ROS output, genome instability, and the development of the cancer. Classic approach to target mitochondria of cancerous cells with novel-targeted therapeutics helps in targeting the mitochondrial apoptotic proteins and changing energy metabolism. Key benefit of selective drug delivery is it reduces the toxicity of drug and increases specificity. Better understanding of mitochondrial role in tumor growth will help to design more therapeutic agents with better selectivity. � Springer Nature Singapore Pte Ltd. 2022.
Targeting mitochondria as a potential therapeutic strategy against chemoresistance in cancer
(Elsevier Masson s.r.l., 2023-02-09T00:00:00) Mukherjee, Soumi; Bhatti, Gurjit Kaur; Chhabra, Ravindresh; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
The importance of mitochondria is not only limited to energy generation but also in several physical and chemical processes critical for cell survival. Mitochondria play an essential role in cellular apoptosis, calcium ion transport and cellular metabolism. Mutation in the nuclear and mitochondrial genes, altered oncogenes/tumor suppressor genes, and deregulated signalling for cell viability are major reasons for cancer progression and chemoresistance. The development of drug resistance in cancer patients is a major challenge in cancer treatment as the resistant cells are often more aggressive. The drug resistant cells of numerous cancer types exhibit the deregulation of mitochondrial function. The increased biogenesis of mitochondria and its dynamic alteration contribute to developing resistance. Further, a small subpopulation of cancer stem cells in the heterogeneous tumor is primarily responsible for chemoresistance and has an attribute of mitochondrial dysfunction. This review highlights the critical role of mitochondrial dysfunction in chemoresistance in cancer cells through the processes of apoptosis, autophagy/mitophagy, and cancer stemness. Mitochondria-targeted therapeutic strategies might help reduce cancer progression and chemoresistance induced by various cancer drugs. � 2023