Browsing by Author "Brijesh Kumar Singh"

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Mucuna pruriens in Parkinson’s and in some other diseases: recent advancement and future prospective
(Springer Science and Business Media Deutschland GmbH, 2020) Sachchida Nand Rai; Vivek K. Chaturvedi; Payal Singh; Brijesh Kumar Singh; M.P. Singh
Mucuna pruriens (Mp) is an annual and perennial legume which belongs to the family Fabaceae having different types of therapeutic activity. Anti-oxidative, anti-inflammatory, anti-epileptic, anti-microbial, etc. are the example of some most common activities of Mp. It is widely utilized as a potent aphrodisiac. The anti-Parkinsonian activity of Mp was explored since the nineteenth century. The neuroprotective activity of Mp was shown by several researchers. Levodopa (L-DOPA) is the important constituents responsible for the anti-Parkinsonian activity of Mp. Apart from L-DOPA, several other important bioactive components like Ursolic acid (UA) and Betulinic acid (BA) also exhibit a similar neuroprotective activity. Parkinson’s disease (PD) is mainly sporadic. A very small proportion shows the genetic nature of PD. The anti-Parkinsonian activity of Mp was explored in different toxin-induced PD models as like MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), Rotenone, Paraquat, 6-hydroxydopamine (6-OHDA) as suggested by several pieces of literature. Various parts of Mp’s like seed, leaf, and stem exhibit potent neuroprotective attributes. Among different parts, seeds are widely utilized as anti-PD agents because of the higher percentage of L-DOPA. Besides anti-PD activity, Mp’s neuroprotective potential was also explored in the ischemic model of stroke that also shows positive results. Recently, several clinical trials have been performed on the anti-PD activity of Mp on PD patients that show convincing results. Although, a small population-based study needs to be further validated in the broader population. Apart from anti-PD activity, Mp also shows its therapeutic activity in some other diseases like cancer, diabetes, skin infection, anemia, antihypertensive, etc. that are summarized in Table 1. In this review, we have discussed the anti-PD potential of Mp in the sporadic and genetic model along with some clinical trials that have performed on PD patients. Some other activity of Mp is also summarized in this review. There is a strong need to test the efficacy of Mp in some other neurodegenerative diseases along with PD. Following this, this review emphasizes the role of Mp in PD systematically through literature analysis available to date.Table 1Ashidi et al. (2019)Anosike et al. (2018)Pinto et al. (2019)Ulu et al. (2018)Saiyad Musthafa et al. (2018)Seppan et al. (2018)Sinha et al. (2018)Khan and Kumar (2017) © 2020, King Abdulaziz City for Science and Technology.
Promising drug targets and associated therapeutic interventions in Parkinson's disease
(Wolters Kluwer Medknow Publications, 2021) Sachchida Nand Rai; Payal Singh; Ritu Varshney; Vivek K. Chaturvedi; Emanuel Vamanu; M.P. Singh; Brijesh Kumar Singh
Parkinson's disease (PD) is one of the most debilitating brain diseases. Despite the availability of symptomatic treatments, response towards the health of PD patients remains scarce. To fulfil the medical needs of the PD patients, an efficacious and etiological treatment is required. In this review, we have compiled the information covering limitations of current therapeutic options in PD, novel drug targets for PD, and finally, the role of some critical beneficial natural products to control the progression of PD. © 2021 Wolters Kluwer Medknow Publications. All rights reserved.
Quality Control in Huntington’s Disease: a Therapeutic Target
(Springer New York LLC, 2019) Sachchida Nand Rai; Brijesh Kumar Singh; Aaina Singh Rathore; Walia Zahra; Chetan Keswani; Hareram Birla; Saumitra Sen Singh; Hagera Dilnashin; Surya Pratap Singh
Huntington’s disease (HD) is a fatal autosomal dominantly inherited brain disease caused by excessively expanded CAG repeats in gene which encodes huntingtin protein. These abnormally encoded huntingtin proteins and their truncated fragments result in disruption of cellular quality mechanism ultimately triggering neuronal death. Despite great efforts, a potential causative agent leading to genetic mutation in HTT, manifesting the neurons more prone to oxidative stress, cellular inflammation, energy depletion and apoptotic death, has not been established yet. Current scenario concentrates on symptomatic pathologies to improvise the disease progression and to better the survival. Most of the therapeutic developments have been converged to rescue the protein homeostasis. In HD, abnormal expansion of glutamine repeats in the protein huntingtin leads to toxic aggregation of huntingtin which in turn impairs the quality control mechanism of cells through damaging the machineries involved in removal of aggregated abnormal protein. Therapeutic approaches to improve the efficiency of aggregate clearance through quality control mechanisms involve protein folding machineries such as chaperones and protein degradation machineries such as proteasome and autophagy. Also, to reduce protein aggregation by enhancing proper folding, to degrade and eliminate the aggregates are suggested to negatively regulate the HD progression associated with the disruption of protein homeostasis. This review focuses on the collection of therapeutic strategies targeting enhancement of protein quality control activity to delay the HD pathogenesis. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
The Role of PI3K/Akt and ERK in Neurodegenerative Disorders
(Springer New York LLC, 2019) Sachchida Nand Rai; Hagera Dilnashin; Hareram Birla; Saumitra Sen Singh; Walia Zahra; Aaina Singh Rathore; Brijesh Kumar Singh; Surya Pratap Singh
Disruption of Akt and Erk-mediated signal transduction significantly contributes in the pathogenesis of various neurodegenerative diseases (NDs), such as Parkinson’s disease, Alzheimer’s diseases, Huntington’s disease, and many others. These regulatory proteins serve as the regulator of cell survival, motility, transcription, metabolism, and progression of the cell cycle. Therefore, targeting Akt and Erk pathway has been proposed as a reasonable approach to suppress ND progression. This review has emphasized on involvement of Akt/Erk cascade in the neurodegeneration. Akt has been reported to regulate neuronal toxicity through its various substrates like FOXos, GSK3β, and caspase-9 etc. Akt is also involved with PI3K in signaling pathway to mediate neuronal survival. ERK is another kinase which also regulates proliferation, differentiation, and survival of the neural cell. There has also been much progress in developing a therapeutic molecule targeting Akt and Erk signaling. Therefore, improved understanding of the molecular mechanism behind the regulatory aspect of Akt and Erk networks can make strong impact on exploration of the neurodegenerative disease pathogenesis. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.