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Mitochondrial Dysfunction Leads to Several Neurodegenerative DisordersBY: Geetanjali Murari | Category: Healthcare | Submitted: 2013-10-02 11:01:12
Article Summary: "This article states about the physiology responsible for neurodegenerative disorders like, Alzheimer's disease which is a fatal and widely spread disease across the world..."
Alzheimer's disease is a fatal neurodegenerative disorder. The aggregation of ß-amyloid proteins (senile plaques) and neurofibrillary tangles lead to damaged neuronal cells. It affects the cognition ability of a person in the later part of their life. The disease is coming like a cyclone across the globe. The percentage of aging population being affected by this disease is increasing astonishingly. The average life expectancy of human is escalating due to the developing socio-economic condition. Subsequently, age associated brain disorders are also increasing in the older population. Most of the brain disorders (Alzheimer's, Parkinson's, etc.) are detected with clinical symptoms in later stage but the inception of those disease related causal processes is initiated much earlier.
The mitochondria play a very important role in our brain. It produces energy and generates free oxygen radicals called as oxyradicals which are harmful for neurons. The generation of free radicals increases oxidative stress level in the brain. The brain has large amount of antioxidants as its defense against these free radicals.The semi-independent mitochondria produce energy in the form of ATP and free radicals. Brain requires high oxygen flow for proper functioning. More than 90% of oxygen is utilized by the mitochondria to generate ATP (Adenosine Triphosphate) and they are converted into oxyradicals that increases the oxidative burden inside the brain. These free ions are highly reactive and could destroy the neurons. To protect our brain, antioxidants are present as a defense against these free radicals. Brain has its own de-novo synthesis of antioxidants. The oxyradicals attack the biomolecules within which results into oxidative damage around the cell.
Oxygen is highly important for our body and brain. The neuronal cells completely depend upon aerobic respiration for their survival due to their limited glycolytic capacity. Hence, during hypoxic-hypoxia condition at higher altitudes, neurons start damaging. So, population at higher altitudes is prone towards dementia. People should intake more antioxidants like, omega3 in their diet to reduce the risk.
Mitochondria are damaged in neurodegenerative disorders. The dysfunction in mitochondria leads to less production of ATP and higher production of free radicals (ROS). The enzymatic production is also hampered in the process. The damaged mitochondria are less efficient producers of two key enzymes (alpha-ketoglutarate dehydrogenase and Pyruvate dehydrogenase complexes) which participate in the rate-limiting steps of TCA/Kreb's cycle in mitochondria. The impaired energy metabolism due to lower ATP production contributes in oxidative stress which ultimately results in programmed cell death (apoptosis).
The microglial cells in the brain are migratory and have phagocytic functions. The oligomerization of AB and amyloid precursor proteins leads to the activation of microglia and has implications in AD. These activated microglial cells are involved in inflammation and produces neurotoxic effects which is associated with neurodegeneration. The activated microglia over-expresses cytokines (IL-1) in the brain regions of AD patients. This over-expression of interleukin leads to tau phophorylation that aids in tangle formation which is a physiology of the disorder. The activated microglia will secrete proteases, cytokines, and reactive oxygen species (ROS). The free radicals (oxyradicals) enhance the aggregation of ß-amyloid (Aß) in the plaque formation. The growing size of these plaques activates more microglia, which then secretes more cytokines, proteases, and reactive oxygen species, thus increasing the severity of the Alzheimer's disease.
Now, we have an innovative brain imaging technique which can diagnose the disorder at a very early stage. This would aid in arresting the disease and increasing the quality of life of the person suffering from the disorder. The unique Magnetic Resonance Spectroscopy (MRS) technique aids in determining the parameters which can act as a diagnostic biomarker for neurodegenerative disorders. The imaging technique can detect the anti-oxidant (glutathione) level in different brain regions. The sharp fall in the glutathione level depicts the stressed condition of the brain. Thus, the chemical analysis of our brain could help in the early diagnostic of fatal diseases. This will help in increasing the quality and quantity of our life.
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