Pharmacology - Research Publications

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    Neuroprotective effect of silymarin against 3-Nitropropionic acid-induced neurotoxicity in rats
    (Elsevier B.V., 2022-09-20T00:00:00) Chandolia, Priyanka; Rahi, Vikrant; Kumar, Puneet
    (HD) Huntington's disease is a severe hereditary catastrophic neurological disease with an autosomal dominant heritable changes manifested by cognitive, behavioural, and motor progression deficits, resulting in death. Several mechanisms are involved in the pathogenesis of this complex and rare disease, including excitotoxicity, mitochondrial dysfunction, neurotransmitters imbalance, and oxidative stress. Silymarin was selected as an investigational drug, due to its numerous activities in current research, it possesses substantial antioxidant and neuroprotective functionalities. The present research attempts, i.p. injections of 3-NPA (10 ?mg/kg) were given for 21 days to trigger Huntington-like symptoms in rats. The percentage fluctuations in body weight, the footfall counts, and the time required to transverse the beam and motor functions were analyzed at multiple time points. Oxidative stress markers like MDA/LPO, GSH, protein, nitrite, catalase, and superoxide dismutase levels were examined in the striatum region. The current study results conclusively demonstrate that chronic 3-NPA administration significantly decreased the body weight and showed marked abnormalities in motor coordination, locomotion, and increased striatal generation of free radicals. Furthermore, treatment with silymarin (100 & 200 ?mg/kg/p.o.), mitigated 3-NPA triggered behavioural and biochemical alterations. Our study results could conclude that Silymarin may be advantageous and might develop an adjuvant treatment for the management of Huntington's disease. � 2022 The Authors
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    Caspase-mediated regulation of the distinct signaling pathways and mechanisms in neuronal survival
    (Elsevier B.V., 2022-06-16T00:00:00) Khan, Heena; Bangar, Annu; Grewal, Amarjot Kaur; Bansal, Puneet; Singh, Thakur Gurjeet
    Caspases are intimately associated with altering various signaling pathways, resulting in programmed cell death or apoptosis. Apoptosis is necessary for the normal homeostasis of cells and their development. The untoward activation of apoptotic pathways indirectly or directly results in pathologies of various diseases. Identifying different caspases in apoptotic pathways directed the research to develop caspase inhibitors as therapeutic agents. However, no drug is available in the market that targets caspase inhibition and produces a therapeutic effect. Here, we will shed light on the role of caspases in the number of neuronal disorders and neurodegenerative diseases. The article reviews the findings about the activation of various upstream mechanisms associated with caspases in neurodegenerative disorders along with the recent progress in the generation of caspase inhibitors and the challenge faced in their development as therapeutic agents for neurological indications. � 2022 Elsevier B.V.
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    Recent Advances in Molecular Pathways and Therapeutic Implications Targeting Mitochondrial Dysfunction for Alzheimer�s Disease
    (Springer, 2021-11-02T00:00:00) Dhapola, Rishika; Sarma, Phulen; Medhi, Bikash; Prakash, Ajay; Reddy, Dibbanti HariKrishna
    Alzheimer�s disease (AD) is a neurodegenerative disorder which leads to mental deterioration due to aberrant accretion of misfolded proteins in the brain. According to mitochondrial cascade hypothesis, mitochondrial dysfunction is majorly involved in the pathogenesis of AD. Many drugs targeting mitochondria to treat and prevent AD are in different phases of clinical trials for the evaluation of safety and efficacy as mitochondria are involved in various cellular and neuronal functions. Mitochondrial dynamics is regulated by fission and fusion processes mediated by dynamin-related protein (Drp1). Inner membrane fusion takes place by OPA1 and outer membrane fusion is facilitated by mitofusin1 and mitofusin2 (Mfn1/2). Excessive calcium release also impairs mitochondrial functions; to overcome this, calcium channel blockers like nilvadipine are used. Another process acting as a regulator of mitochondrial function is mitophagy which is involved in the removal of damaged and non-functional mitochondria however this process is also altered in AD due to mutations in Presenilin1 (PS1) and Amyloid Precursor Protein (APP) gene. Mitochondrial dynamics is altered in AD which led to the discovery of various fission protein (like Drp1) inhibitors and drugs that promote fusion. Modulations in AMPK, SIRT1 and Akt pathways can also come out to be better therapeutic strategies as these pathways regulate functions of mitochondria. Oxidative phosphorylation is major generator of Reactive Oxygen Species (ROS) leading to mitochondrial damage; therefore reduction in production of ROS by using antioxidants like MitoQ, Curcumin and Vitamin Eis quiteeffective. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.