scholarly journals Therapeutic Potential of Vital Transcription Factors in Alzheimer’s and Parkinson’s Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy

2021 ◽  
Vol 15 ◽  
Author(s):  
Sachchida Nand Rai ◽  
Neeraj Tiwari ◽  
Payal Singh ◽  
Divya Mishra ◽  
Anurag Kumar Singh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Neurodegenerative Disorders ◽  
Structural Integrity ◽  
Therapeutic Potential ◽  
Transcription Factor Eb ◽  
Autophagy Pathway ◽  
Common Observation

Autophagy is an important cellular self-digestion and recycling pathway that helps in maintaining cellular homeostasis. Dysregulation at various steps of the autophagic and endolysosomal pathway has been reported in several neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington disease (HD) and is cited as a critically important feature for central nervous system (CNS) proteostasis. Recently, another molecular target, namely transcription factor EB (TFEB) has been explored globally to treat neurodegenerative disorders. This TFEB, is a key regulator of autophagy and lysosomal biogenesis pathway. Multiple research studies suggested therapeutic potential by targeting TFEB to treat human diseases involving autophagy-lysosomal dysfunction, especially neurodegenerative disorders. A common observation involving all neurodegenerative disorders is their poor efficacy in clearing and recycle toxic aggregated proteins and damaged cellular organelles due to impairment in the autophagy pathway. This dysfunction in autophagy characterized by the accumulation of toxic protein aggregates leads to a progressive loss in structural integrity/functionality of neurons and may even result in neuronal death. In recent years TFEB, a key regulator of autophagy and lysosomal biogenesis, has received considerable attention. It has emerged as a potential therapeutic target in numerous neurodegenerative disorders like AD and PD. In various neurobiology studies involving animal models, TFEB has been found to ameliorate neurotoxicity and rescue neurodegeneration. Since TFEB is a master transcriptional regulator of autophagy and lysosomal biogenesis pathway and plays a crucial role in defining autophagy activation. Studies have been done to understand the mechanisms for TFEB dysfunction, which may yield insights into how TFEB might be targeted and used for the therapeutic strategy to develop a treatment process with extensive application to neurodegenerative disorders. In this review, we explore the role of different transcription factor-based targeted therapy by some natural compounds for AD and PD with special emphasis on TFEB.

scholarly journals Imaging Familial and Sporadic Neurodegenerative Disorders Associated with Parkinsonism

2021 ◽  
Author(s):  
David J. Brooks
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Lewy Body Dementia ◽  
Imaging Biomarkers ◽  
Imaging Findings ◽  
Subclinical Disease ◽  
Similarities And Differences ◽  
Potential Use

AbstractIn this paper, the structural and functional imaging changes associated with sporadic and genetic Parkinson’s disease and atypical Parkinsonian variants are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed, and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression is debated. Imaging changes associated with nonmotor complications of PD are presented. The similarities and differences in imaging findings in Lewy body dementia, Parkinson’s disease dementia, and Alzheimer’s disease are discussed.

scholarly journals Mitochondrial Dynamics and Mitophagy in the 6-Hydroxydopamine Preclinical Model of Parkinson's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Maria F. Galindo ◽  
Maria E. Solesio ◽  
Sandra Atienzar-Aroca ◽  
Maria J. Zamora ◽  
Joaquín Jordán Bueso
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Therapeutic Potential ◽  
Mitochondrial Dynamics ◽  
Second Messengers ◽  
Treatment Strategies ◽  
Preclinical Model ◽  
Molecular Signaling ◽  
Mitochondrial Division

We discuss the participation of mitochondrial dynamics and autophagy in the 6-hydroxidopamine-induced Parkinson’s disease model. The regulation of dynamic mitochondrial processes such as fusion, fission, and mitophagy has been shown to be an important mechanism controlling cellular fate. An imbalance in mitochondrial dynamics may contribute to both familial and sporadic neurodegenerative diseases including Parkinson’s disease. With special attention we address the role of second messengers as the role of reactive oxygen species and the mitochondria as the headquarters of cell death. The role of molecular signaling pathways, for instance, the participation of Dynamin-related protein 1(Drp1), will also be addressed. Furthermore evidence demonstrates the therapeutic potential of small-molecule inhibitors of mitochondrial division in Parkinson’s disease. For instance, pharmacological inhibition of Drp1, through treatment with the mitochondrial division inhibitor-1, results in the abrogation of mitochondrial fission and in a decrease of the number of autophagic cells. Deciphering the signaling cascades that underlie mitophagy triggered by 6-OHDA, as well as the mechanisms that determine the selectivity of this response, will help to better understand this process and may have impact on human treatment strategies of Parkinson’s disease.

scholarly journals Role and Mechanism of Vitamin A Metabolism in the Pathophysiology of Parkinson’s Disease

2021 ◽  
pp. 1-22
Author(s):  
Anaıs Marie ◽  
Morgane Darricau ◽  
Katia Touyarot ◽  
Louise C. Parr-Brownlie ◽  
Clémentine Bosch-Bouju
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Dopaminergic Neurons ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Vitamin A Metabolism ◽  
Health And Wellbeing

Evidence shows that altered retinoic acid signaling may contribute to the pathogenesis and pathophysiology of Parkinson’s disease (PD). Retinoic acid is the bioactive derivative of the lipophilic vitamin A. Vitamin A is involved in several important homeostatic processes, such as cell differentiation, antioxidant activity, inflammation and neuronal plasticity. The role of vitamin A and its derivatives in the pathogenesis and pathophysiology of neurodegenerative diseases, and their potential as therapeutics, has drawn attention for more than 10 years. However, the literature sits in disparate fields. Vitamin A could act at the crossroad of multiple environmental and genetic factors of PD. The purpose of this review is to outline what is known about the role of vitamin A metabolism in the pathogenesis and pathophysiology of PD. We examine key biological systems and mechanisms that are under the control of vitamin A and its derivatives, which are (or could be) exploited for therapeutic potential in PD: the survival of dopaminergic neurons, oxidative stress, neuroinflammation, circadian rhythms, homeostasis of the enteric nervous system, and hormonal systems. We focus on the pivotal role of ALDH1A1, an enzyme expressed by dopaminergic neurons for the detoxification of these neurons, which is under the control of retinoic acid. By providing an integrated summary, this review will guide future studies on the potential role of vitamin A in the management of symptoms, health and wellbeing for PD patients.

scholarly journals Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Smijin K. Soman ◽  
Ruben K. Dagda
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Development ◽  
Structural Integrity ◽  
Intermembrane Space ◽  
Loss Of Function ◽  
Serine Threonine Kinase ◽  
Functional Roles ◽  
Neuronal Functions

Mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson’s disease (PD). Consistent with this concept, loss of function mutations in the serine/threonine kinase- PINK1 (PTEN-induced putative kinase-1) causes autosomal recessive early onset PD. While the functional role of f-PINK1 (full-length PINK1) in clearing dysfunctional mitochondria via mitophagy is extensively documented, our understanding of specific physiological roles that the non-mitochondrial pool of PINK1 imparts in neurons is more limited. PINK1 is proteolytically processed in the intermembrane space and matrix of the mitochondria into functional cleaved products (c-PINK1) that are exported to the cytosol. While it is clear that posttranslational processing of PINK1 depends on the mitochondria’s oxidative state and structural integrity, the functional roles of c-PINK1 in modulating neuronal functions are poorly understood. Here, we review the diverse roles played by c-PINK1 in modulating various neuronal functions. Specifically, we describe the non-canonical functional roles of PINK1, including but not limited to: governing mitochondrial movement, neuronal development, neuronal survival, and neurogenesis. We have published that c-PINK1 stimulates neuronal plasticity and differentiation via the PINK1-PKA-BDNF signaling cascade. In addition, we provide insight into how mitochondrial membrane potential-dependent processing of PINK1 confers conditional retrograde signaling functions to PINK1. Further studies delineating the role of c-PINK1 in neurons would increase our understanding regarding the role played by PINK1 in PD pathogenesis.

scholarly journals Role of Tridosha Siddhanta in the management of Kampavata w.s.r.t Parkinsonism

2021 ◽  
Vol 9 (01) ◽  
Author(s):  
Dr. Ansari Huma ◽  
Dr. Pravin Patil
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Equilibrium State ◽  
Old Age ◽  
Neurodegenerative Disorders ◽  
Modern Science ◽  
The Other ◽  
Prevalent Disease ◽  
Diet And Lifestyle

 Ayurveda holistic science is based on entities like dosha, dhatu, and mala. Tridosha (i.e.vata, pitta, kapha) maintains health in an equilibrium state, and imbalance in these dosha develops diseased conditions in individuals. Vata is the only dosha that presides over all the other entities. In the present era, vatavyadhi is the most prevalent disease due to stress, improper sleep, improper diet and lifestyle, and old age. In Ayurveda, various nanatmaja vyadhi of vata has been explained, kampavata vyadhi is one of them. By comparing kampavata vyadhi with modern science most of the clinical features of this disease resemble Parkinson's disorder. Parkinson's disease is a group of progressive neurodegenerative disorders characterized by rest tremor, bradykinesia, muscular rigidity, shuffling gait, and flexed posture.     Hence, the endeavor is made to understand the concept of Tridosha Siddhanta in kampavata vyadhi and turn in the perspective of Parkinson's disease with the Ayurvedic approach.    

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