Pharmacology - Research Publications

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

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    Calcium channelopathies in neurodegenerative disorder: an untold story of RyR and SERCA
    (Taylor and Francis Ltd., 2023-11-16T00:00:00) Dhureja, Maanvi; Arthur, Richmond; Soni, Divya; Upadhayay, Shubham; Temgire, Pooja; Kumar, Puneet
    Introduction: Recent neuroscience breakthroughs have shed light on the sophisticated relationship between calcium channelopathies and movement disorders, exposing a previously undiscovered tale focusing on the Ryanodine Receptor (RyR) and the Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA). Calcium signaling mainly orchestrates neural communication, which regulates synaptic transmission and total network activity. It has been determined that RyR play a significant role in managing neuronal functions, most notably in releasing intracellular calcium from the endoplasmic reticulum. Areas covered: It highlights the involvement of calcium channels such as RyR and SERCA in physiological and pathophysiological conditions. Expert opinion: Links between RyR and SERCA activity dysregulation, aberrant calcium levels, motor and cognitive dysfunction have brought attention to the importance of RyR and SERCA modulation in neurodegenerative disorders. Understanding the obscure function of these proteins will open up new therapeutic possibilities to address the underlying causes of neurodegenerative diseases. The unreported RyR and SERCA narrative broadens the understanding of calcium channelopathies in movement disorders and calls for more research into cutting-edge therapeutic approaches. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    An Overview of the Pathophysiological Mechanisms of 3-Nitropropionic Acid (3-NPA) as a Neurotoxin in a Huntington's Disease Model and Its Relevance to Drug Discovery and Development
    (Springer, 2023-02-04T00:00:00) Upadhayay, Shubham; Yedke, Narhari Gangaram; Rahi, Vikrant; Singh, Surbhi; Kumar, Sachin; Arora, Anchal; Chandolia, Priyanka; Kaur, Prabhsharan; Kumar, Mandeep; Koshal, Prashant; Jamwal, Sumit; Kumar, Puneet
    Animal models are used to better understand the various mechanisms involved in the pathogenesis of diseases and explore potential pathways that will aid in discovering therapeutic targets. 3-Nitropropionic Acid (3-NPA) is a neurotoxin used to induce Huntington's disease (HD)-like symptoms in experimental animals. The 3-NPA is a fungus toxin that impairs the complex II (succinate dehydrogenase) activity of the mitochondria and reduces ATP synthesis, leading to excessive production of free radicals resulting in the degeneration of GABAergic medium spiny neurons (MSNs) in the striatum. This is characterized by motor impairments a key clinical manifestation of HD. 3-NPA has the potential to alter several cellular processes, including mitochondrial functions, oxidative stress, apoptosis, and neuroinflammation mimicking HD-like pathogenic conditions in animals. This review strives to provide a new insight towards the 3-NPA induced molecular dysfunctioning in developing an animal model of HD. Moreover, we summarise several preclinical studies that support the use of the 3-NPA-induced models for drug discovery and development in HD. This review is a collection of various articles that were published from 1977 to 2022 on Pubmed (1639), Web of Science (2139), and Scopus (2681), which are related to the 3-NPA induced animal model. Graphical Abstract: [Figure not available: see fulltext.] � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Repurposing artemisinins as neuroprotective agents: a focus on the PI3k/Akt signalling pathway
    (Springer Science and Business Media Deutschland GmbH, 2022-12-05T00:00:00) Arthur, Richmond; Navik, Umashanker; Kumar, Puneet
    Artemisinin and its derivatives, since their discovery by professor Tu Youyou in the early 1970s, have been the bedrock for the management of malaria globally. Recent works have implied that they could be used to manage other diseases including neurodegenerative disorders. Neurodegenerative disorders mainly occur in the adult population resulting from a progressive deterioration of neuronal structures. These include Parkinson�s disease (PD), Alzheimer�s disease (AD), Huntington�s disease (HD), and Multiple sclerosis (MS), among others. The PI3K/Akt signaling pathway plays a significant role in the central nervous system. It has been investigated extensively for its role in central nervous system physiological processes such as cell survival, autophagy, neuronal proliferation, and synaptic plasticity. Therefore, the modulation of this pathway will be crucial in the management of neurodegenerative disorders. This review seeks to compile most of the research findings on the possible neuroprotective role of artemisinins with special emphasis on their modulatory role on the PI3k/Akt pathway. A literature survey was conducted on PubMed, EBSCO, Web of Science, and EMBASE using the keyword artemisinins, and a total of 10,281 articles were retrieved from 1956 to 2022. Among these, 120 articles were examined using Mesh words like PI3k/Akt, neurodegeneration, and neuroinflammation coupled with boolean operators. Most research revealed that artemisinins could help neurodegenerative disorders by modulating the PI3k/Akt with subsequent inhibition of oxidative stress, neuroinflammation, and apoptosis. This paper illustrates that artemisinins could be repurposed as a neuroprotective agent. � 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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    Ferulic acid ameliorates neurodegeneration via the Nrf2/ARE signalling pathway: A Review
    (Elsevier B.V., 2022-10-30T00:00:00) Singh, Surbhi; Arthur, Richmond; Upadhayay, Shubham; Kumar, Puneet
    Background: Ferulic acid is a polyphenolic phytoconstituent synthesized from the metabolism of amino acids phenylalanine and tyrosine found in fruits and vegetables. Neurodegenerative disorders have been a thorn in the flesh of neuroscientists owing in part to the increase in the aged population. Several drugs used in the management of these disorders are either ineffective or come with unbearable side effects. We present a review of ferulic acid focusing on leveraging its antioxidant property in an attempt to explain its role in neurodegenerative disorders. Basic procedure: data were obtained by perusing scientific databases including Web of Science and PubMed. It was realised that 18,000 articles were associated with ferulic acid from 1960-to 2022. We narrowed it down using the keywords neuroprotection, and antioxidant of which we had 239 articles. Main findings: results indicated that ferulic acid has wide neuropharmacological applications due to its antioxidant, anti-inflammatory, neuroprotective and antiapoptotic effects among others. The neuroprotective effect of ferulic acid has been studied in many diseases like Alzheimer's, Epilepsy, and Parkinson's disease. Principal conclusion: the neuroprotective potential of FA may be due to its ability to absorb active forms of oxygen and nitrogen and use redox-bearing compounds to regulate genetic expression including, encoding for antioxidant enzymes, the anti-apoptotic protein family Bcl-2, and pro-survival neurotrophic factors like BDNF. Its higher bioavailability and lipophilic nature make it a better drug candidate than other polyphenols for neurological disorders. � 2022 The Author(s)
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    Mitochondria-targeted drug delivery systems for the effective treatment of neurodegenerative disorders
    (Elsevier, 2022-03-18T00:00:00) Khare, Vaishali; Gupta, Surbhi; Bisht, Preeti; Garabadu, Debapriya
    Mitochondria are known to be the powerhouse of the cell. Its dysfunction leads to several alterations in cellular physiology. Mitochondrial dysfunction is a well-documented process in the pathophysiology of neurodegeneration and neurodegenerative disorders. The interplay between mitochondrial dysfunction and oxidative stress is well suggested in the pathophysiology of neurodegenerative disorders. The activation of autophagy is also well established along with the mitochondrial impairment in neurodegenerative disorders. The relationship between mitochondrial dysfunction and excitotoxicity is also well established in the pathophysiology of neurodegenerative disorders. Enhanced apoptosis and necrosis is well established along with mitochondrial dysfunction in the pathophysiology of neurodegenerative disorders. Several synthetic and herbal drugs have been established in the management of mitochondrial dysfunction-induced neurodegenerative disorders. Little information is available about the formulations of the established mitochondria-targeted drugs in the management of neurodegenerative disorders. Therefore, critical attention is required in the development of mitochondria-targeted drug delivery systems for therapeutic and diagnostic applications in neurodegenerative disorders. � 2022 Elsevier Inc. All rights reserved.
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    Neuroprotective role of apocynin against pentylenetetrazole kindling epilepsy and associated comorbidities in mice by suppression of ROS/RNS
    (Elsevier B.V., 2021-11-30T00:00:00) Jaiswal, Gagandeep; Kumar, Puneet
    Epilepsy is a neurological disease that transpires due to the unusual synchronized neuronal discharge within the central nervous system, which drives repetitious unprovoked seizures. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a complex enzyme accountable for reactive oxygen species (ROS) production, neurodegeneration, neurotoxicity, memory impairment, vitiates normal cellular processes, long term potentiation, and thus, implicated in the pathogenesis of epilepsy. Therefore, the present study was sketched to examine the neuroprotective effect of apocynin, NADPH oxidase inhibitor in pentylenetetrazole kindling epilepsy, and induced comorbidities in mice. Mice (either sex) were given pentylenetetrazole (35 mg/kg, i.p.) every other day up to 29 days, and a challenge test was executed on the 33rd day. Pretreatment with apocynin (25, 50, and 100 mg/kg, i.p.) was carried out from 1st to 33rd day. Rotarod and open field test were performed on the 1st, 10th, 20th, and 30th days of the study. Animals were tutored on the morris water maze from 30th to 33rd day, and the retention was registered on the 34th day. Tail suspension test and elevated plus maze were sequentially performed on the 32nd and 33rd day of the study. On the 34th day, animals were sacrificed, and their brains were isolated to conduct biochemical estimation. NADPH oxidase activation due to chronic pentylenetetrazole treatment resulted in generalized tonic-clonic seizures, enhanced oxidative stress, remodeled neurotransmitters' level, and resulted in comorbidities (anxiety, depression, and memory impairment). Pretreatment with apocynin significantly restricted the pentylenetetrazole induced seizure severity, ROS production, neurotransmitter alteration, and comorbid conditions by inhibiting the NADPH oxidase enzyme. � 2021