Order Your Paper From the most reliable Essay writing Service. 

.

 

Parkinson’s Disease is the second most common neurodegenerative disease, after Alzheimer’s. Onset typically occurs late in life, affecting approximately 1% of 65 year olds, with the prevalence increasing to 4-5% by age 85 (Dawson & Dawson 2003). There are also rare cases of early-onset Parkinson’s, which are usually familial. Research into the gene mutations discovered in such hereditary cases has also contributed to the understanding of the aetiology of the spontaneous, late onset form of the disease.

Parkinson’s Disease (PD) is characterized clinically by tremors at rest, bradykinesia (slowness of voluntary movement), muscle rigidity, decrease in postural reflex and facial expression and an altered gait (Kumar et al. 2005). A subset of patients (10-15%) also develop dementia. Symptoms are progressive and result in decreased mobility and eventually severe disability.

The symptomatic motor disturbances arise from the progressive loss of dopaminergic neurons in the substantia nigra of the brain. This results in a decrease in the dopaminergic content of the striatum. These areas play an important role in modulating feedback from the thalamus to the motor cortex.

AIMS AND OBJECTIVES

This report aims to investigate the current knowledge of the aetiology of PD, by examining evidence in the literature. It is crucial to understand the pathological mechanisms underlying the selective destruction of dopaminergic neurons in PD so that effective treatments and prophylaxis can be developed.

PROPOSED STRATEGY

Researchers have studied the molecular mechanisms of PD pathogenesis using a number of techniques: in vitro tissue cultures of human and animal neurons, post-mortem human brain tissue, mouse models of the disease, genetic studies and more novel techniques such as the use of ‘cybrids’. Evidence from all of these will be amalgamated and conclusions drawn.

MOLECULAR PATHOGENESIS OF PD

That PD is generally associated with old age must be considered an important clue when trying to elucidate the causal mechanism of PD. The same is also true of the most common neurodegenerative disease, Alzheimer’s Disease (AD). Both are also characterised by an accumulation of protein aggregates resulting in progressive neuronal loss, suggesting a common underlying pathology.

Histological brain sections of PD patients shows characteristic, large inclusion bodies in the cytosol of surviving neurons of the substantia nigra, as well as locus ceruleus and surrounding brainstem nuclei, called Lewy bodies (Kumar et al. 2005). These are aggregates of -synuclein (Spillantini et al. 1997), a protein whose gene (SYN, aka PARK 1) has been linked to familial PD (Athanassiadou et al. 1999), as well as other proteins such as ubiquitin and synphilin-1. It is unclear whether these aggregates contribute to the pathogenesis, are a simple by-product or even part of an attempted protective mechanism, described as the aggresome theo