Alpha‐synuclein at the nexus of genes and environment: the impact of environmental enrichment and stress on brain health and disease

• Published in: Journal of neurochemistry 2019-09, Vol.150 (5), p.591-604
• Main Authors: Wassouf, Zinah, Schulze‐Hentrich, Julia M.
• Format: Article
• Language: English
• Subjects: Aging; alpha-Synuclein - deficiency; alpha-Synuclein - genetics; alpha-Synuclein - physiology; alpha‐synuclein; Animal models; Animals; Brain; Brain - metabolism; Brain - pathology; Diseases in Twins - genetics; enriched environment; Enrichment; Environmental aspects; Environmental effects; Environmental factors; Environmental impact; Environmental stress; Epigenesis, Genetic; epigenetics; Gene-Environment Interaction; Health risks; Humans; Lewy Bodies - metabolism; Longitude; Mice; Mice, Knockout; Mimicry; Motor Activity; Movement disorders; Mutation; neurodegeneration; Neurodegenerative diseases; Parkinson Disease - genetics; Parkinson's disease; Parkinsonian Disorders - etiology; Parkinsonian Disorders - genetics; Pesticides - toxicity; Physical Stimulation; Protein Aggregation, Pathological - genetics; Protein Aggregation, Pathological - metabolism; Review; REVIEW ARTICLES; Risk analysis; Risk Factors; stress; Stress, Physiological; Stress, Psychological - complications; Synuclein; Synucleinopathies - etiology; Synucleinopathies - genetics; Synucleinopathies - metabolism; Transducers
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.14787

Accumulation of alpha‐synuclein protein aggregates is the hallmark neuropathologic feature of synucleinopathies such as Parkinson’s disease. Rare point mutations and multiplications in SNCA, the gene encoding alpha‐synuclein, as well as other genetic alterations are linked to familial Parkinson’s disease cases with high penetrance and hence constitute major genetic risk factors for Parkinson’s disease. However, the preponderance of cases seems sporadic, most likely based on a complex interplay between genetic predispositions, aging processes and environmental influences. Deciphering the impact of these environmental factors and their interactions with the individual genetic background in humans is challenging and often requires large cohorts, complicated study designs, and longitudinal set‐ups. In contrast, rodent models offer an ideal system to study the influence of individual environmental aspects under controlled genetic background and standardized conditions. In this review, we highlight findings from studies examining effects of environmental enrichment mimicking stimulation of the brain by its physical and social surroundings as well as of environmental stressors on brain health in the context of Parkinson’s disease. We discuss possible internal molecular transducers of such environmental cues in Parkinson’s disease rodent models and emphasize their potential in developing novel avenues to much‐needed therapies for this still incurable disease. This article is part of the Special Issue “Synuclein” The central role of alpha‐synuclein in the etiology of Parkinson’s disease is based on genetics and neuropathology. While familial cases are rare, the preponderance of cases seems sporadic, most likely based on a complex interplay between genetic predispositions, aging processes and environmental influences. In this review, we discuss results from recent studies investigating the impact of environmental enrichment mimicking stimulation of the brain by its physical and social surroundings as well as of environmental stressors using rodent models of Parkinson’s disease. This article is part of the Special Issue “Synuclein”