Biochemical and Molecular Pathogenetic Mechanisms behind Causation of Parkinson’s Disease
Parkinson’s disease (PD) is an age-related neurodegenerative disorder that affects approximately 1 million persons in the United States. It is characterized by resting tremor, rigidity, bradykinesia, gait disturbance and postural instability. Its pathological features include degeneration of dopaminergic neurons in the substantia nigra pars compacta coupled with intracytoplasmic inclusions known as Lewy bodies. Neurodegeneration and Lewy bodies can also be found in locus ceruleus, nucleus basalis, hypothalamus, cerebral cortex, cranial nerve motor nuclei, and central & peripheral components of autonomic nervous system. The appearance of Lewy-body-like inclusions in nigrostriatal terminals might be followed by retrograde degeneration, further accumulation of aggregated proteins in nigral cell bodies and, finally, reactive gliosis and cell death. In familial forms of Parkinson’s disease, linked to mutations in α-synuclein, it is proposed that a loss of normal function of this protein, as well as a toxic effect of altered forms of the mutant protein, promote the accumulation of dopamine in cytoplasm. This would result in oxidative stress, leading to the onset of neurodegenerative changes mentioned above. Finally, we review evidence for a role of α-synuclein in synaptic vesicle recycling& suggest that impaired function of this protein might lead to accumulation of dopamine in cytoplasm. This could be the final deleterious event that triggers the death of nigral dopaminergic neurons in PD. In addition to prevailing pharmacologic therapies and surgical procedures,Yoga can be one of the most beneficial complementary therapies for PD patients, which canact at molecular level to reduce oxidative stress, improve neuro-cognition, boost their mood, enhance sensory-motor performance, increase dopamine & serotonin secretion and reduce cortisol secretion, thereby collectively enhancing quality of life of PD patients & their care-takers.
Author (s) Details
C. S. Nagalakshmi
Professor and Head, Department of Biochemistry, Sri Siddhartha Institute of Medical Sciences & Research Centre, T Begur, Bangalore Rural, Karnataka, India.
N. U. Santhosh
Consultant Neurosurgoen, Aster CMI Hospital, Sahakaranagar, Hebbal, Bangalore, Karnataka, India
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alpha synuclein alternate therapy apoptosis biochemical biomarker complementary therapy dopamine excitotoxicity genetics inflammation mechanisms mitochondrial dysfunction molecular MPTP oxidative stress Parkinson’s disease pathogenetic quality of life yoga