09-04-2014, 01:52 AM
(This post was last modified: 09-04-2014, 02:18 AM by Administrator.)
Parkinson's disease (PD) is coming up as a global concern in the current fast paced lifestyle. Let me focus a bit on the common causes and gene clusters responsible for PD, though it is still not very clear.
PD is a neurodegenerative disease which has become quite common in the modern world. It is very much fatal and incurable. Though several genes have been identified, whose mutation may result in PD (or similar disease), but still the disease is quite irregular and the origin is unknown. The chief genes whose alteration of the molecular pathways leads to cell degeneration are leucine-rich repeat kinase 2 (LRRK2), α-synuclein (SNCA), PTEN-induced putative kinase 1 (PINK1), DJ-1 and parkin. Recent works gave some insight of these gene functions indicating protein phosphorylation, abnormal protein buildup, mitochondrial dysfunction and oxidative stress are common pathways to PD pathogenesis. But the exact reason behind the disease is still not clear and thus the cure is also out of reach.
No doubt, both environmental factors and genetic makeup are responsible for PD in the modern world. Association of PD and oxidative stress is quite clear and is established as a common cause. Postmortem examination illustrates decreased complex I activity & reduced glutathione (GSH) levels and increased levels of iron. In the presymptomatic stage of PD GSH levels get decreased, which may be a mainly responsible constituent of the cascade of events leading to cell death. It may also directly make neurons susceptible to the actions of toxins or induce nigral cell degeneration. Several studies proposed that the origination of oxidative stress might have taken place in the glial cells instead of in neurons. This modification in glial function may be a significant factor to the pathological development that occurs in PD.
In PD oxidative stress induced injury take place in the brain, and is evident by the increase in DNA damage and lipid peroxidation at the substantia nigra. At the same time there is also an apparent increase in protein oxidation in various parts of the brain. This further indicates the more widespread pathologic course happening in PD to which the substantia nigra is predominantly susceptible.
The substantia nigra cannot handle damaged or mutant proteins and this situation lead to aggregation and deposition of these proteins forming Lewy bodies which are primarily responsible for dementia. This can be proved easily as Lewy bodies stain for both α-synuclein and nitrated proteins. Recent studies made it possible to propose that the failure to process structurally modified proteins in different components of the brain, creating oxidative stress is the major reason of both familial and sporadic PD.
PD is a neurodegenerative disease which has become quite common in the modern world. It is very much fatal and incurable. Though several genes have been identified, whose mutation may result in PD (or similar disease), but still the disease is quite irregular and the origin is unknown. The chief genes whose alteration of the molecular pathways leads to cell degeneration are leucine-rich repeat kinase 2 (LRRK2), α-synuclein (SNCA), PTEN-induced putative kinase 1 (PINK1), DJ-1 and parkin. Recent works gave some insight of these gene functions indicating protein phosphorylation, abnormal protein buildup, mitochondrial dysfunction and oxidative stress are common pathways to PD pathogenesis. But the exact reason behind the disease is still not clear and thus the cure is also out of reach.
No doubt, both environmental factors and genetic makeup are responsible for PD in the modern world. Association of PD and oxidative stress is quite clear and is established as a common cause. Postmortem examination illustrates decreased complex I activity & reduced glutathione (GSH) levels and increased levels of iron. In the presymptomatic stage of PD GSH levels get decreased, which may be a mainly responsible constituent of the cascade of events leading to cell death. It may also directly make neurons susceptible to the actions of toxins or induce nigral cell degeneration. Several studies proposed that the origination of oxidative stress might have taken place in the glial cells instead of in neurons. This modification in glial function may be a significant factor to the pathological development that occurs in PD.
In PD oxidative stress induced injury take place in the brain, and is evident by the increase in DNA damage and lipid peroxidation at the substantia nigra. At the same time there is also an apparent increase in protein oxidation in various parts of the brain. This further indicates the more widespread pathologic course happening in PD to which the substantia nigra is predominantly susceptible.
The substantia nigra cannot handle damaged or mutant proteins and this situation lead to aggregation and deposition of these proteins forming Lewy bodies which are primarily responsible for dementia. This can be proved easily as Lewy bodies stain for both α-synuclein and nitrated proteins. Recent studies made it possible to propose that the failure to process structurally modified proteins in different components of the brain, creating oxidative stress is the major reason of both familial and sporadic PD.
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