Molecular Etiology of Parkinson Disease: Recent Progress

Abstract

Parkinson disease (PD) is one of the most widespread neurodegenerative disorders. In North America alone it affects 1 million people. It is a multifactorial disorder caused by genetic, various biological and environmental factors. One of the important features of PD is the dementia, which is believed to be due to the loss of dopaminergic neurons. In some cases the disease can be inherited as an autosomal dominant or recessive trait but in the majority of cases it is acquired. The biological causes of the disorder are unknown. The identification of mutations in the parkin gene in the autosomal recessive case and alpha-synuclein gene in autosomal dominant cases has opened a new avenue for studies to understand the basic biochemical mechanisms of pathogenesis. Although several types of treatments such as transplantation of cells that produce L-Dopa and direct gene delivery using adeno-associated viral vectors may correct animal models of PD, their usefulness in the human is not yet clear. A better understanding of the causes of neurodegeneration may lead to better therapies in the future.

Imbalanced estrogen metabolism in the brain: possible relevance to the etiology of Parkinson’s disease

“…The hallmark of PD is the specific and progressive degeneration of nigrostriatal dopamine neurons and depletion of dopamine (DA) (Shastry 2000, Dauer & Przedborski 2003, Huang et al 2003). PD symptoms are apparent only after loss of dopaminergic neurons in the substantia nigra is at least 50%, leading to more than 80% reduction in dopamine levels in the striatum (Lang & Lozano 1998, Deumens et al 2002).…”

“…PD symptoms are apparent only after loss of dopaminergic neurons in the substantia nigra is at least 50%, leading to more than 80% reduction in dopamine levels in the striatum (Lang & Lozano 1998, Deumens et al 2002). Several causal mechanisms have been postulated regarding the neuronal degeneration that occurs in PD (Figure 1) (Lang & Lozano 1998, Shastry 2000, Deumens et al 2002, Dauer & Przedborski 2003, Huang et al 2003). These include genetic factors, mitochondrial dysfunction, environmental toxins, and oxidative stress (Steece-Collier et al 2002, Henchcliffe & Beal 2008, Hatcher et al 2008, Chinta & Andersen 2008).…”