Genes and the Environment in Neurodegeneration

Abstract

Neurodegenerative diseases are a heterogeneous group of pathologies which includes complex multifactorial diseases, monogenic disorders and disorders for which inherited, sporadic and transmissible forms are known. Factors associated with predisposition and vulnerability to neurodegenerative disorders may be described usefully within the context of gene-environment interplay. There are many identified genetic determinants for neurodegeneration, and it is possible to duplicate many elements of recognized human neurodegenerative disorders in animal models of the disease. However, there are similarly several identifiable environmental influences on outcomes of the genetic defects; and the course of a progressive neurodegenerative disorder can be greatly modified by environmental elements. In this review we highlight some of the major neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and prion diseases.) and discuss possible links of gene-environment interplay including, where implicated, mitochondrial genes.

A Case–Control Study on the Origin of Atypical Scrapie in Sheep, France

“…Organophosphates and pyrethroids were frequently identifi ed among reported products; these 2 groups of active components, which may be associated with Parkinson disease (21,36), interfere with the mitochondrial chain, which is a possible pathway for prion diseases (37). Another study on toxic exposures and gene-environment interaction could be more conclusive regarding this issue (38). In that regard, fl ocks recently exposed to insecticide treatment for control of bluetongue vectors could constitute interesting cohorts to follow up for atypical scrapie.…”

Contribution of hypoxia to Alzheimer’s disease: is HIF-1α a mediator of neurodegeneration?

“…It is now apparent that genetic predisposition is accountable for only a small number of AD cases. Fully penetrant mutations leading to protein cleavage and consequent aggregation are responsible for only 5% of all AD cases and result in familial early onset AD (from 65 years) [16]. Although most cases have no known genetic basis, exposure to other pathogenic conditions, including chronic inflammation, traumatic brain injury, cerebrovascular disease, hypoxia/ischemia and exposure to pesticides [5,[16][17][18], could be contributing factors.…”

Spatial Clusters of Creutzfeldt-Jakob Disease Mortality in Japan between 1995 and 2004

“…This is evidence that has never been reported before in such previous studies as clinical case studies, regional epidemiological surveys and geographical analyses at the prefectural level [10,12,[26][27][28] . Although we cannot clarify how the disease has been transmitted there because of a lack of genetic and clinical information on patients who died from CJD, we suggest the existence of some endogenous or exogenous factors for CJD common to these areas: PRNP mutation, migration of PRNP mutant carriers, repeated pointsource outbreaks of infection, gene-gene or gene-environment interactions, and iatrogenic transmission [7,9,25,[29][30][31][32] . Four of 8 hot-spot areas detected for males appeared in a part of the cluster for females as well, which, however, was not statistically significant.…”