ReviewNeurodegenerative signaling factors and mechanisms in Parkinson's pathology
Graphical abstract
Mechanism involved in PD pathology. Pictorial presentation showing the involvement of different neurodegenerative mechanisms like oxidative stress, genetic mutations, endoplasmic reticulum (ER) stress, mitochondrial dysfunction and apoptosis in dopaminergic neurons after exposure to environmental factors/neurotoxins.
Section snippets
Parkinson's disease: overview
PD is a devastating degenerative neurological illness without cure. It includes clinical characteristics like tremor, rigidity, postural instability, bradykinesia and akinesia. Tremor is the most common and well-known symptom of PD. Although around 30% of the PD patients do not have tremor at disease onset, but the disease progression involves their development. Rigidity is an excessive and continuous contraction of the muscles which produces stiffness as well as resistance to joints movement,
Protein aggregation
Protein aggregation is a biological phenomenon which involves intracellular or extracellular accumulation of misfolded proteins (Maiti et al., 2014). Such protein aggregates are the pathological hallmark of PD pathology involving accumulation of α-synuclein (α-syn) protein in the form of Lewy bodies. Mutations in specific genes like parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2), DJ-1, alpha-synuclein, PTEN-induced putative kinase 1 (PINK1) and P-type ATPase gene-ATP13A2 have also been
Antioxidant supply
Reactive oxygen species produced under physiological conditions are in very low levels and easily neutralized by endogenous antioxidant defense system which includes the antioxidant enzymes such as glutathione reductase (GRd), glutathione peroxidise (GPx), superoxide dismutase (SOD), catalase and the antioxidant reduced glutathione (GSH). GSH is a critical molecule in resisting oxidative stress and maintaining the reducing environment of the cell (Meister, 1988). Reduction in the levels of
Promising brain drug delivery to Parkinson disease
Recently, there has been an increasing interest in the development of new drug delivery systems for PD therapeutics. Available therapy like L-Dopa is targets the motor symptoms but it neither treat the neurodegenerative process nor provide neuroprotection to the surviving dopaminergic neurons (Deierborg et al., 2008). Thus, current research efforts are focused on halting neurodegeneration using promising alternatives such as antioxidants, anti-apoptotic agents, cell-based therapies and
Conclusion
PD is a complicated multifaceted disease with many causative factors involved in its pathogenesis. To date numbers of signaling pathways have been suggested in disease pathology but still it remains elusive prompting us to investigate further. The studies in last more than two decades have removed the broader outlines of disease etiology and it appears that only the fine lines remain to be removed. Brain is the most mysterious organ in human body and nothing can be said before investigation.
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Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease
2021, Experimental GerontologyCitation Excerpt :It is widely accepted that neuroinflammation acts as the key factor during the process of PD. The inflammatory factors, superoxide, and NO are then massively generated, aggravating neuroinflammation and causing damage of the dopamine neurons (Felice et al., 2016; Goswami et al., 2017; Lull and Block, 2010). Various studies have shown a connection between the gut and the PD occurrence.
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2021, Neuroscience LettersEffect of hemodynamic characteristic changes of the carotid artery on 6-OHDA-induced Parkinson's disease model rats treated by Gut-acupuncture
2020, Journal of King Saud University - Science“Effect of valerenic acid on neuroinflammation in a MPTP-induced mouse model of Parkinson's disease”
2020, IBRO ReportsCitation Excerpt :PD is the main neuromotor pathology that develops due to the prominent loss of dopaminergic neurons in substantia nigra pars compacta, which causes dopamine deficiency (Poewe et al., 2017; Ray Dorsey et al., 2018). The molecular mechanisms of the pathogenesis of PD are diverse, resulting in subtypes of the disease, and they include proteinopathy related to α-synuclein (misfolding and aggregation contributing to Lewy bodies and neurites), oxidative stress, mitochondrial dysfunction and neuroinflammation, which feeds neurotoxic processes (Tansey and Goldberg, 2011; Ganguly et al., 2017; Goswami et al., 2017). Neuroinflammation is an important part of PD development, and microglia play a role in the degradation of α-synuclein and neuronal debris by phagocytosis, which is neuroprotective in balanced activation.