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PHARMASPIRE - Volume 11, Issue 4, October - December, 2019

Pages: 97-106
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Novel targets for mitochondria dysfunction and oxidative stress in Parkinson’s disease

Author: Karamjeet Kaur, Taranjit Singh, Dilpreet Kaur, Sania Grover, Shamsher Singh

Category: Pharmaceutics


Parkinson is a progressive neurological disorder affecting neurons of basal ganglia. It generally consists of slowing down in initiation and execution of muscle movements generally characterized by tremors, muscle rigidity, bradykinesia, and gait abnormalities. Most of the cases of Parkinson’s disease are idiopathic, but it is likely a result of interaction among aging, genetic factors, and environmental factors. The genes responsible for Parkinson can be alpha-synuclein (SNCA), PTEN-induced kinase 1, PARK8, etc. Autosomal dominant forms of Parkinson are associated with mutation of α-syn (PARK 1&4) and Leucine-rich repeat kinase 2. The most important factor in pathophysiology can be free radicals and mitochondrial dysfunction which is induced by mutation and deposition of SNCA protein. An increase in the levels of glutamate may also lead to the overproduction of free radicals and reactive oxygen species. Several antioxidants, such as glutathione (GSH), are present in substantia nigra pars compacta region of basal ganglia to limit the damage by free radicals. In the premotor stage of idiopathic Parkinson’s disease, Lewy bodies are initially found in the medulla oblongata and some other regions. As the disease progress, Lewy bodies ascend to the midbrain, especially SNpc. The spread of Lewy body to cortex occurs in the advanced stage. The clinically detectable stage idiopathic Parkinson’s disease is generally after 70–80% damage of the SNC neurons. The available therapies provide symptomatic benefits and choice of therapy is patient specific. The choice of therapy is much critical for optimizing short- and long-term outcomes.

Keywords: Parkinson’s disease, mitochondrial dysfunction, oxidative stress, alpha-synuclein, Lewy bodies, substantia nigra pars compacta


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