Parkinson Disease Genetic

Parkinson's disease

Abstract

Parkinson's disease is the second common neurodegenerative disorder. The main characteristics of the disease are muscle rigidity, tremors, and weakness of emotional expressions. The literature explains many etiologies of the disease, disturbance of dopaminergic neurotransmission, neurodegenerative changes of the substantia nigra and genetic mutations are possible causes. The aim of this essay is to describe in brief what causes Parkinson's disease.

Parkinson's disease

Parkinson's disease, named after James Parkinson who first described the disorder in 1817, is a disturbance of motor function. Slowing and weakness of emotional and voluntary movements, muscular rigidity, and tremors are the main characteristics of the disease. A multiplicity of different pathological conditions produces Parkinson's disease and the main pathological changes are due to lesions of the corpus striatum and substantia nigra (Brain and Walton, 1969).

Parkinson's disease is the second most common neurodegenerative disorder (second to Alzheimer disease). It affects 1% of Americans above the age of 60 years (as it is rare before the age of 40). Disease incidence is higher in males, with no race or ethnic difference. The main pathological features of the disease are disturbances of the dopamine dependent neuro-transmission, presence of Lewy bodies in the remaining neurons of the substantia nigra. Recently genetic evidence of Parkinson's disease etiology has been suggested (Nutt and Wooten, 2005).

Parkinson's disease and disturbances of dopaminergic neurotransmission

The corpus striatum and the substantia nigra:

The corpus striatum is, phylogenetically, the oldest part of the cerebrum. It lies deep in the substance of the cerebral hemisphere between the lateral ventricle and the insula. It contains numerous fibers among which are the efferent fibers running from the corpus striatum to the substantia nigra. The substantia nigra is a grey mass lying between the crus cerebri and tegmentum of the midbrain at the level of the superior colliculi. It consists of a zona compacta lying dorsally, and a zona reticulate. This part of the brain is responsible for the control of muscle tone, posture and muscle tone (extrapyramidal functions). The neurotransmitter for the neurons that pass from the substantia nigra to the corpus striatum (dorsal part) is dopamine. These neurons are responsible for the commencement and carrying out of movements (Volkow and others, 1996).

The dopaminergic deficiency theory of Parkinson's disease:

It assumes that the main characteristic symptoms of Parkinson's disease (muscle rigidity, tremors and postural instability) are the product of the marked disappearance of the dopaminergic neurons in the zona compacta of the substantia nigra because of cell death. Dopamine neurons in the ventral tegmental area are responsible for motivation, mood, and thought orderliness, thus dopamine deficiency explains the psychological disturbances occasionally present in Parkinson's disease patients Moore and others, 2005).

Mechanisms of neurodegenerative changes (Biological changes)

Genetics of Parkinson's disease

The observation that 10 to 15 % of Parkinson's disease patients have positive family history for relatives of the first or second-degree suffering from the disease pointed out to study possible genetic factors of the disease (Nutt and Wooten, 2005). Mutant genes on chromosome four responsible for the control of alpha synuclein protein (in dopamine secreting nerve cells) may be the cause of autosomal dominant Parkinson's disease. Failing genes on chromosome six, responsible for the control of parkin molecule (needed for cell self-destruction of alpha synuclein) may be responsible for autosomal recessive Parkinson's disease. Research suggests that in cases with positive maternal history of Parkinson's disease, nerve cells mitochondria DNA defects are worthy of further investigation. A mutant tau gene has been recently described; this gene control controls the support system responsible for transferring nutrients through nerve cells. This gene defect may be specifically responsible for late (old age) onset Parkinson's disease (Klein and Schlossmacher, 2006).

Conclusion

References

Brain, L and Walton, J N. (1969). Brain's Diseases of the Nervous System (7th edition). London: The English Language Book Society and Oxford University Press.

Klein C. and Schlossmacher, M G. (2006). The Genetics of Parkinson Disease: Implications for Neurological Care. Nat Clin Pract Neurol, 2(3), 136.

Moore, D J., West, A B., Dawson, V L. and Dawson, T M. (2005). Molecular Pathophysiology of Parkinson's Disease. Annu. Rev. Neurosci., 28, 57-87.

Nutt, J G. and Wooten, G. F. (2005). Diagnosis and Initial Management Of Parkinson's Disease. N Engl J Med, 352, 1021-7.

Volkow, N D., Fowler, J S., Gatley, S J. et al (1996). PET Evaluation of the Dopamine System of the Human Brain. J Nucl Med, 37, 1242-1256.