Parkinson's disease : from pathogenesis to novel therapeutic approaches

Abstract

Parkinson's Disease (PD) ranks as the second most common neurodegenerative disorder (1). The main site affected is the substantia nigra pars compacta (SNpc) in the midbrain, which suffers a relentless degeneration of dopaminergic neurons of the nigrostriatal pathway, hence resulting in a lack of the neurotransmitter dopamine (DA) in the basal ganglia. Both genetic and environmental factors contribute to the aetiology of the disease (2). Few (10-15%) cases are familial and single gene mutations give rise to less than 5% of PD forms -monogenic (Mendelian inheritance) (3). The genes SNCA, LRRK2 and VPS35, are autosomal dominant, whereas Parkin, PINKl and DJ-1 are autosomal recessive. Recently, glucocerebrosidase (GBA) gene mutations have been found to be a prime genetic risk factor for PD (4). In fact, heterozygous loss of function of GBA causes more than a five-fold increase in the probability of developing PD (5). Apart from genetic predisposition, age is a major risk factor for PD. Its incidence climbs up with age to almost 100 per 100,000 person years, between 70 and 79 years (5). The median age of onset is 60 years (5). Substantial evidence shows that a 3:2 ratio of men to women exist s (2). In contrast to familial PD, the aetiology of idiopathic PD is multifactorial, as it is the product of an interplay of components: multiple genes, environment and life style - caffeine, smoking and pesticides are among the most strongly associated with PD (3). Moreover, consumption of tea (rich source of polyphenolic compounds), is associated with neuroprotective and neurodegenerative effects in PD, although further studies are needed (6).