Human Genetics And Molecular Medicine - Research Publications
Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/107
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Item 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 SinghNeurodegenerative 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. � 2023Item 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 SinghParkinson'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.Item Clinical Strategies and Therapeutics for Human Monkeypox Virus: A Revised Perspective on Recent Outbreaks(Multidisciplinary Digital Publishing Institute (MDPI), 2023-07-12T00:00:00) Ghosh, Nilanjan; Chacko, Leena; Vallamkondu, Jayalakshmi; Banerjee, Tanmoy; Sarkar, Chandrima; Singh, Birbal; Kalra, Rajkumar Singh; Bhatti, Jasvinder Singh; Kandimalla, Ramesh; Dewanjee, SaikatAn enveloped double-stranded DNA monkeypox virus (MPXV) is a causative agent of the zoonotic viral disease, human monkeypox (HMPX). MPXV belongs to the genus Orthopoxviridae, a family of notorious smallpox viruses, and so it shares similar clinical pathophysiological features. The recent multicountry HMPX outbreak (May 2022 onwards) is recognized as an emerging global public health emergency by the World Health Organization, shunting its endemic status as opined over the past few decades. Re-emergence of HMPX raises concern to reassess the present clinical strategy and therapeutics as its outbreak evolves further. Keeping a check on these developments, here we provide insights into the HMPX epidemiology, pathophysiology, and clinical representation. Weighing on its early prevention, we reviewed the strategies that are being enrolled for HMPX diagnosis. In the line of expanded MPXV prevalence, we further reviewed its clinical management and the diverse employed preventive/therapeutic strategies, including vaccines (JYNNEOS, ACAM2000, VIGIV) and antiviral drugs/inhibitors (Tecovirimat, Cidofovir, Brincidofovir). Taken together, with a revised perspective of HMPX re-emergence, the present report summarizes new knowledge on its prevalence, pathology, and prevention strategies. � 2023 by the authors.Item Protective effects of a mitochondria-targeted small peptide SS31 against hyperglycemia-induced mitochondrial abnormalities in the liver tissues of diabetic mice, Tallyho/JngJ mice(Elsevier B.V., 2021-02-25T00:00:00) Bhatti, Jasvinder Singh; Tamarai, Kavya; Kandimalla, Ramesh; Manczak, Maria; Yin, Xiangling; Ramasubramanian, Bhagavathi; Sawant, Neha; Pradeepkiran, Jangampalli Adi; Vijayan, Murali; Kumar, Subodh; Reddy, P. HemachandraType 2 Diabetes mellitus (T2DM) has become a major public health issue associated with a high risk of late-onset Alzheimer's disease (LOAD). Mitochondrial dysfunction is one of the molecular events that occur in the LOAD pathophysiology. The present study was planned to investigate the molecular alterations induced by hyperglycemia in the mitochondria of diabetic mice and further explore the possible ameliorative role of the mitochondria-targeted small peptide, SS31 in diabetic mice. For this purpose, we used a polygenic mouse model of type 2 diabetes, TALLYHO/JngJ (TH), and nondiabetic, SWR/J mice strains. The diabetic status in TH mice was confirmed at 8 weeks of age. The 24 weeks old experimental animals were segregated into three groups: Non-diabetic controls (SWR/J mice), diabetic (TH mice) and, SS31 treated diabetic TH mice. The mRNA and protein expression levels of mitochondrial proteins were investigated in all the study groups in the liver tissues using qPCR and immunoblot analysis. Also, the mitochondrial functions including H2O2 production, ATP generation, and lipid peroxidation were assessed in all the groups. Mitochondrial dysfunction was observed in TH mice as evident by significantly elevated H2O2 production, lipid peroxidation, and reduced ATP production. The mRNA expression and Western blot analysis of mitochondrial dynamics (Drp1 and Fis1 � fission; Mfn1, Mfn2, and Opa1 -fusion), and biogenesis (PGC-1?, Nrf1, Nrf2, and TFAM) genes were significantly altered in diabetic TH mice. Furthermore, SS31 treatment significantly reduced the mitochondrial abnormalities and restore mitochondrial functions in diabetic TH mice. � 2019 Elsevier B.V. and Mitochondria Research Society. All rights reserved.Item Mitochondria-Targeted Small Peptide, SS31 Ameliorates Diabetes Induced Mitochondrial Dynamics in Male TallyHO/JngJ Mice(Springer, 2020-10-07T00:00:00) Bhatti, Jasvinder Singh; Thamarai, Kavya; Kandimalla, Ramesh; Manczak, Maria; Yin, Xiangling; Kumar, Subodh; Vijayan, Murali; Reddy, P. HemachandraThe escalating burden of type 2 diabetes (T2D) and its related complications has become a major public health challenge worldwide. Substantial evidence indicates that T2D is one of the culprits for the high prevalence of Alzheimer�s disease (AD) in diabetic subjects. This study aimed to investigate the possible mitochondrial alterations in the pancreas induced by hyperglycemia in diabetes. We used a diabetic TallyHO/JngJ (TH) and non-diabetic, SWR/J mice strains. The diabetic and non-diabetic status in animals was assessed by performing intraperitoneal glucose tolerance test at four time points, i.e., 4, 8, 16, and 24�weeks of age. We divided 24-week-old TH and SWR/J mice into 3 groups: controls, diabetic TH mice, and diabetic TH mice treated with SS31 peptide. After the treatment of male TH mice with SS31, intraperitoneally, for 4�weeks, we studied mitochondrial dynamics, biogenesis, and function. The mRNA and protein expression levels of mitochondrial proteins were evaluated using qPCR and immunoblot analysis. The diabetic mice after 24�weeks of age showed overt pancreatic injury as demonstrated by disintegration and atrophy of ? cells with vacuolization and reduced islet size. Mitochondrial dysfunction was observed in TH mice, as evidenced by significantly elevated H2O2 production, lipid peroxidation, and reduced ATP production. Furthermore, mRNA expression and immunoblot analysis of mitochondrial dynamics genes were significantly affected in diabetic mice, compared with controls. However, treatment of animals with SS31 reduced mitochondrial dysfunction and restored most of the mitochondrial functions and mitochondrial dynamics processes to near normal in TH mice. In conclusion, mitochondrial dysfunction is established as one of the molecular events that occur in the pathophysiology of T2D. Further, SS31 treatment may confer protection against the mitochondrial alterations induced by hyperglycemia in diabetic TallyHO/JngJ mice. � 2020, Springer Science+Business Media, LLC, part of Springer Nature.