Department of Pharmacy
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Item Exploration of the therapeutic potential of the epigenetic modulator decitabine on 6-OHDA-induced experimental models of Parkinson’s disease(ACS, 2025-04) Taliyan, RajeevParkinson’s disease (PD) poses a global menace, as the available treatment methods solely aim to mitigate symptoms. An effective strategy to address the pathogenesis of PD involves eliminating the accumulation of aggregated alpha-synuclein, emphasizing the role of epigenetics. Aberrant epigenetic changes significantly influence gene expression, which is pivotal in PD progression, impacting neuronal growth and degeneration. Epigenetic-related genes are regulated by histone modification and DNA methylation processes. Nevertheless, their significance in PD has not been confirmed. This research was carried out using both in vitro and in vivo approaches. In the in vitro investigations, N2A neuronal cell lines were utilized, and the neuroprotective effect of decitabine (DB) was observed at concentrations of 0.1 μM and 0.5 μM. In the in vivo study, PD induction led to significant motor deficits, which were notably ameliorated at the highest treatment dose. This improvement was accompanied by a marked attenuation of inflammatory mediators, including TNF-α, IL-6, IL-1β, and CRP levels. Additionally, there was a significant enhancement in antioxidative defense, evidenced by increased GSH (glutathione) levels and reduced oxidative stress marker NO (nitric oxide). Neurochemical analysis revealed a substantial rise in dopamine levels, a critical PD marker, alongside an elevation in BDNF, indicating neuroprotective effects. Furthermore, gene expression analysis indicated a notable upregulation in the mRNA expression of epigenetic genes and proteins linked to PD pathology. Histological assessments, including IHC, H&E, and CV staining of the substantia nigra, showed enhanced structural integrity following treatment. Collectively, these insights reveal DB’s promise as a therapeutic solution for mitigating PD symptoms and pathology exacerbated by 6-OHDA.Item Neuroprotective effects of the epigenetic modulator decitabine in 6-OHDA-Induced cellular and mouse models of Parkinson's disease(Elsevier, 2025-05) Taliyan, RajeevOxidative stress is one of the factors in Parkinson’s disease (PD) etiology. Genes implicated in PD, such as DJ-1, PARKIN and PINK1, contribute to oxidative stress, affecting dopaminergic neurons. The Xlinked G6PD gene encodes glucose 6-phosphate dehydrogenase, an important regulator of oxidative stress. Conflicting reports have shown both reduced G6PD activity and elevated G6PD expression levels in PD patients, leading to inconsistent conclusions about its role in PD.Item Epigenetic mechanisms linking environmental exposure to Parkinson’s disease: a comprehensive review(Elsevier, 2025-10) Taliyan, RajeevParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunction and non-motor symptoms affecting cognition, mood and autonomic function. Both genetic susceptibility and environmental exposures such as pesticides (e.g., paraquat, rotenone), heavy metals (e.g., manganese, lead), tobacco smoke, and caffeine have been implicated in PD pathogenesis. Recent studies highlight the role of epigenetic mechanisms including DNA methylation (e.g., SNCA, PARK2), histone modifications (e.g., H3K9me3, H3K27ac), and microRNAs (e.g., miR-133b, miR-7), in mediating the effects of environmental toxins on neuronal function and survival. These alterations can disrupt transcriptional programs, impair mitochondrial function and promote oxidative stress, neuroinflammation and dopaminergic neuronal loss. Aging further compounds epigenetic dysregulation by reducing chromatin plasticity and enhancing glial reactivity. This review synthesizes current insights into how specific environmental exposures modulate the epigenetic landscape in PD and explores their downstream effects on key pathological processes. We also discuss emerging therapeutic strategies targeting epigenetic modifiers such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and miRNA-based interventions. A clearer understanding of the gene environment epigenome interface may help identify early biomarkers and develop precision medicine approaches for PD.Item Epigenetics in neurodegeneration: emerging biomarkers and translational insights(Elsevier, 2025-12) Taliyan, RajeevNeurodegenerative disorders (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are characterized by progressive neuronal loss leading to cognitive, motor, and behavioral impairments. Despite available interventions such as medications, physical therapy, and surgery, effective disease-modifying therapies remain elusive, with most treatments limited to symptom management. The multifactorial etiology of NDDs involves genetic, environmental, and increasingly recognized epigenetic factors that alter gene expression and drive disease onset and progression. Epigenetic mechanisms such as DNA methylation, histone modification, and chromatin remodeling play central roles in neuronal development, brain aging, and neurodegeneration. Recent advances highlight the potential of epigenetic biomarkers as diagnostic and prognostic tools, enabling early detection, monitoring of disease progression, and evaluation of therapeutic response. Protein- and microRNA-based biomarkers in biofluids, including blood and cerebrospinal fluid, provide promising insights into disease pathology and may support precision medicine approaches. This review explores current progress in identifying and validating epigenetic biomarkers and discusses their therapeutic implications, underscoring their transformative potential for improving diagnosis and treatment strategies in NDDs.Item Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease(ACS, 2023-02) Taliyan, RajeevParkinson’s disease is the second most prevalent neurological disease after Alzheimer’s. Primarily, old age males are more affected than females. The aggregates of oligomeric forms of α-synuclein cause the loss of dopaminergic neurons in the substantia nigra pars compacta. Further, it leads to dopamine shortage in the striatum region. According to recent preclinical studies, environmental factors like pesticides, food supplements, pathogens, etc. enter the body through the mouth or nose and ultimately reach the gut. Further, these factors get accumulated in enteric nervous system which leads to misfolding of α-synuclein gene, and aggregation of this gene results in Lewy pathology in the gut and reaches to the brain through the vagus nerve. This evidence showed a strong bidirectional connection between the gut and the brain, which leads to gastrointestinal problems in Parkinson patients. Moreover, several studies reveal that patients with Parkinson experience more gastrointestinal issues in the early stages of the disease, such as constipation, increased motility, gut inflammation, etc. This review article focuses on the transmission of α-synuclein and the mechanisms involved in the link between the gut and the brain in Parkinson’s disease. Also, this review explores the various pathways involved in Parkinson and current therapeutic approaches for the improvement of Parkinson’s disease.Item Neuroprotective Effects of Trehalose and Sodium Butyrate on Preformed Fibrillar Form of α-Synuclein-Induced Rat Model of Parkinson’s Disease(ACS, 2021-07) Taliyan, RajeevTherapeutic options for Parkinson’s disease (PD) are limited to a symptomatic approach, making it a global threat. Targeting aggregated alpha-synuclein (α-syn) clearance is a gold standard for ameliorating PD pathology, bringing autophagy into the limelight. Expression of autophagy related genes are under the regulation by histone modifications, however, its relevance in PD is yet to be established. Here, preformed fibrillar form (PFF) of α-syn was used to induce PD in wistar rats, which were thereafter subjected to treatment with trehalose (tre, 4g/kg, orally), a potent autophagy inducer and sodium butyrate (SB, 300 mg/kg, orally), a pan histone deacetylase inhibitor alone as well as in combination. The combination treatment significantly reduced motor deficits as evidenced after rotarod, narrow beam walk, and open field tests. Novel object location and recognition tests were performed to govern cognitive abnormality associated with advanced stage PD, which was overcome by the combination treatment. Additionally, with the combination, the level of pro-inflammatory cytokines were significantly reduced, along with elevated levels of dopamine and histone H3 acetylation. Further, mRNA analysis revealed that levels of certain autophagy related genes and proteins implicated in PD pathogenesis significantly improved after administration of both tre and SB. Immunofluorescence and H&E staining in the substantia nigra region mirrored a potential improvement after treatment with both tre and SB. Therefore, outcomes of the present study were adequate to prove that combinatorial efficacy with tre and SB may prove to be a formidable insight into ameliorating PD exacerbated by PFF α-syn as compared to its individual efficacy.Item Targeting Histone Deacetylases: A Novel Approach in Parkinson’s Disease(Hindawi Publishing Corporation, 2015) Taliyan, RajeevThe worldwide prevalence of movement disorders is increasing day by day. Parkinson’s disease (PD) is the most common movement disorder. In general, the clinical manifestations of PD result from dysfunction of the basal ganglia. Although the exact underlying mechanisms leading to neural cell death in this disease remains unknown, the genetic causes are often established. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the neurological disease conditions. The acetylation and deacetylation of histone proteins are carried out by opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. In the recent past, studies with HDAC inhibitors result in beneficial effects in both in vivo and in vitro models of PD. Various clinical trials have also been initiated to investigate the possible therapeutic potential of HDAC inhibitors in patients suffering from PD. The possible mechanisms assigned for these neuroprotective actions of HDAC inhibitors involve transcriptional activation of neuronal survival genes and maintenance of histone acetylation homeostasis, both of which have been shown to be dysregulated in PD. In this review, the authors have discussed the putative role of HDAC inhibitors in PD and associated abnormalities and suggest new directions for future research in PD.Item Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: modulation of histone deacetylase activity(Elsevier, 2015-09) Taliyan, RajeevParkinson’s disease (PD) is the second most common neurodegenerative disorder. Recent studies have investigated the involvement of epigenetic modifications in PD. Histone deacetylase (HDAC) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study was designed to investigate the effect of sodium butyrate, a HDAC inhibitor in 6-hydroxydopamine (6-OHDA) – induced experimental PD like symptoms in rats. To produce motor deficit, 6-OHDA was administered unilaterally in the right medial forebrain bundle. Three weeks after 6-OHDA administration, the rats were challenged with apomorphine. Following this, the animals were treated with sodium butyrate (150 and 300 mg/kg i.p.) once daily for 14 days. Movement abnormalities were assessed by battery of behavioral tests. Biochemically, oxidative stress markers, neuroinflammation and dopamine were measured in striatal brain homogenate. Further, to explore the molecular mechanism(s), we measured the level of global H3 histone acetylation and brain derived neurotrophic factor (BDNF). 6-OHDA administration results in significant motor deficit along with reduction in striatal dopamine level. 6-OHDA treated rats showed elevated oxidative stress and neuroinflammatory markers. Treatment with sodium butyrate results in significant attenuation of motor deficits and increased striatal dopamine level. Moreover, sodium butyrate treatment attenuated the oxidative stress and neuroinflammatory markers. These effects occur concurrently with increased global H3 histone acetylation and BDNF levels. Thus, the observed results of the present study are indicative for the therapeutic potential of HDAC inhibitors in PD.Item Dynamin Functions and Ligands: Classical Mechanisms Behind(American Society for Pharmacology and Experimental Therapeutics, 2017-02) Mahesh, R.Dynamin is a GTPase that plays a vital role in clathrin-dependent endocytosis and other vesicular trafficking processes by acting as a pair of molecular scissors for newly formed vesicles originating from the plasma membrane. Dynamins and related proteins are important components for the cleavage of clathrin-coated vesicles, phagosomes, and mitochondria. These proteins help in organelle division, viral resistance, and mitochondrial fusion/fission. Dysfunction and mutations in dynamin have been implicated in the pathophysiology of various disorders, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Charcot-Marie-Tooth disease, heart failure, schizophrenia, epilepsy, cancer, dominant optic atrophy, osteoporosis, and Down’s syndrome. This review is an attempt to illustrate the dynamin-related mechanisms involved in the above-mentioned disorders and to help medicinal chemists to design novel dynamin ligands, which could be useful in the treatment of dynamin-related disorders.