Parkinson's disease risk factors: genetic, environmental, or both?

Abstract

Perhaps one of the most important questions posed by the neurobiology of aging concerns the pathogenic mechanisms in Parkinson's disease (PD). Recently, it was suggested that exposure to pesticides could be the main cause of PD. Another study reported that the environmental endotoxin, lipopolysaccaride produced by Salmonella minnesota, might be a risk factor for PD. An alternative explanation is the genetic component, which has been suggested to be an important risk factor. Epidemiological studies have identified a positive family history of Parkinson as one of the most important risk factors for the disease. However, these studies neither examined nor reviewed the medical records of the family members. The twin study stated that the major factors in the etiology of PD are non-genetic. Meanwhile, epidemiological studies from China have shown that the prevalence of PD is much lower than in the Caucasian population, explained by the low frequency of cytochrome P-450 CYP2D6 debrisoquine hydroxylase gene polymorphism. The etiology of idiopathic PD is still a question for scientists, and calls for further research, especially with the growing proportion of elderly and the rising incidence of PD worldwide. Future research for PD risk factors should consider that multiple interactions occur in PD, resulting in a complex trait, which includes genetic, acquired, and environmental components.

The olfactory vector hypothesis of neurodegenerative disease: Is it viable?

“…It is known, for example, that a mutation in the P450 cytochrome CYP2D6-debrisoquine hydroxylase gene increases the risk for development of PD. 59 Fifth, not all familial cases of PD exhibit smell loss, including some with LRRK2-associated PD. 60 Sixth, aside from interactions between environmental factors and genetic determinants, the heterogeneity of smell loss observed in AD and PD could reflect the following circumstances:…”

Annonamine, a New Aporphine Alkaloid from the Leaves of Annona muricata

“…Therefore, we next evaluated the neurotoxicity against the human neuroblastoma SH-SY5Y which is a well-characterized catecholaminergic cell line often used as a neuronal model in PD research. Among the tested compounds (1)(2)(3)(4)(5) In this study, we have successfully isolated a new aporphine alkaloid together with four known benzylisoquinoline alkaloids from the leaves of A. muricata. It is noteworthy that anonaine (3) has been reported to inhibit dopamine biosynthesis at 0.05 μM by mainly reducing tyrosine hydroxylase activity in rat stable pheochromocytoma cells, PC12.…”

“…6) In this study, we have phytochemically investigated the leaves of the title plant in detail to characterize the chemical constituents especially on alkaloids, because the leaves of A. muricata are used as tea for cardiotonics and it has been known that A. muricata produced benzylisoquinoline type alkaloids. 7,8) The present study describes the isolation and structural elucidation of a new aporphine alkaloid, annonamine (1) together with four known alkaloids (2)(3)(4)(5). The neurotoxicities of these compounds (1)(2)(3)(4)(5) were also investigated against human neuroblastoma cell line, SH-SY5Y.…”

“…1) However, in the case of idiopathic PD (accounting for over 90% of PD cases), endogenous and/or exogenous environmental factors are believed to be crucial for the onset of symptoms. 2,3) In 1999, Caparros-Lefebvre et al suggested the high prevalence of atypical Parkinsonism in the Caribbean Island Guadeloupe was linked with consumption of Annonaceous fruits and herbal tea prepared from Annona muricata and A. squamosa. 4) In 2005, Höglinger et al described the neurotoxic effects of annonacin, the most abundant acetogenin in A. muricata, which inhibited the complex 1 of the mitochondrial respiratory chain.…”

“…CHCl 3 and EtOAcsoluble fractions were combined because of the similarity of TLC pattern. The residue of 1-BuOH-soluble fraction and the combined mixture of CHCl 3 and EtOAc-soluble fractions were subjected to various kinds of column chromatography (CC) to yield five alkaloids (1)(2)(3)(4)(5) (Fig. 1).…”