Pharmacology - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/111

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Author: search.filters.author.Kumari, SnehaHas files: No

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    Nanotherapeutics for Parkinson's disease using metal nanocomposites
    (CRC Press, 2023-10-19T00:00:00) Dhapola, Rishika; Sharma, Prajjwal; Kumari, Sneha; Nagar, Pushank; Medhi, Bikash; Reddy, Dibbanti Harikrishna
    [No abstract available]
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    Endoplasmic reticulum stress in Alzheimer's disease: Molecular mechanisms and therapeutic prospects
    (Elsevier Inc., 2023-07-29T00:00:00) Nagar, Pushank; Sharma, Prajjwal; Dhapola, Rishika; Kumari, Sneha; Medhi, Bikash; HariKrishnaReddy, Dibbanti
    Alzheimer's disease (AD) is a progressive neurodegenerative condition that leads to memory loss and cognitive impairment over time. It is characterized by protein misfolding as well as prolonged cellular stress, such as perturbing calcium homeostasis and redox management. Numerous investigations have proven that endoplasmic reticulum failure may exhibit exacerbation of AD pathogenesis in AD patients, in-vivo and in-vitro models. The endoplasmic reticulum (ER) participates in a variety of biological functions including folding of protein, quality control, cholesterol production, and maintenance of calcium balance. A diverse range of physiological, pathological and pharmacological substances can interfere with ER activity and thus lead to exaggeration of ER stress. The unfolded protein response (UPR), an intracellular signaling network is stimulated due to ER stress. Three stress sensors found in the endoplasmic reticulum, the PERK, ATF6, and IRE1 transducers detect protein misfolding in the ER and trigger UPR, a complex system to maintain homeostasis. ER stress is linked to many of the major pathological processes that are seen in AD, including presenilin1 and 2 (PS1 and PS2) gene mutation, tau phosphorylation and ?-amyloid formation. The role of ER stress and UPR in the pathophysiology of AD implies that they can be employed as potent therapeutic target. This study shows the relationship between ER and AD and how the pathogenesis of AD is influenced by the impact of ER stress. An effective method for the prevention or treatment of AD may involve therapeutic strategies that modify ER stress pathways. � 2023 Elsevier Inc.
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    Apoptosis in Alzheimer�s disease: insight into the signaling pathways and therapeutic avenues
    (Springer, 2023-04-26T00:00:00) Kumari, Sneha; Dhapola, Rishika; Reddy, Dibbanti HariKrishna
    Alzheimer�s disease (AD) is characterized by the accumulation of hyperphosphorylated tau and amyloid-? (A?) protein resulting in synaptic loss and apoptosis. A? and tau deposition trigger apoptotic pathways that result in neuronal death. Apoptosis is considered to be responsible for manifestations associated with AD under pathological conditions. It regulates via extrinsic and intrinsic pathways. It activates various proteins including Bcl-2 family proteins like Bax, Bad, Bid, Bcl-XS, Bcl-XL and caspases comprising of initiator, effector and inflammatory caspases carried out through a cascade of events that finally lead to cell disintegration. The apoptotic elements interact with trophic factors, signaling molecules including Ras-ERK, JNK, GSK-3?, BDNF/TrkB/CREB and PI3K/AKT/mTOR. Ras-ERK signaling is involved in the progression of cell cycle and apoptosis. JNK pathway is also upregulated in AD which results in decreased expression of anti-apoptotic proteins. JAK-STAT triggers caspase-3 mediated apoptosis leading to neurodegeneration. The imbalance between autophagy and apoptosis is regulated by PI3K/Akt/mTOR pathway. GSK-3? is involved in the stimulation of pro-apoptotic factors resulting in dysregulation of apoptosis. Drugs like filgrastim, epigallocatechin gallate, curcumin, nicergoline and minocycline are under development which target these pathways and modulate the disease condition. This study sheds light on apoptotic pathways that are cardinal for neuronal survival and perform crucial role in the occurrence of AD along with the trends in therapeutics targeting apoptosis induced AD. To develop prospective treatments for AD, it is desirable to elucidate potential targets including restoration apoptotic balance, regulation of caspases, Bcl-2 and other crucial proteins involved in apoptosis mediated AD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.