Abstract:

Neurodegenerative disorders like Parkinson’s disease (PD) or atypical Parkinsonian syndromes including the different synucleinopathies and tauopathies are an important burden for patients, relatives,care providers and incur mounting costs for the health care system in our aging society. The lack of disease modifying strategies and the failure in translating promising molecules from bench to bedside is also attributable to a relatively late diagnosis: when patients become symptomatic and seek medical advice, neurodegeneration has already widely spread through the central nervous system and thus represents a major obstacle for disease-modifying and/or regenerative therapies. The detection of neurodegenerative processes at an earlier stage by biomarkers is urgently needed to define state and trait of a disease condition, which ideally would increase precision of diagnosis, allow for stratified therapeutic interventions and monitoring of treatment effects. The mechanisms causing neurodegeneration in aggregation-related disorders like PD are not completely understood but most likely are multifactorial,including factors like oxidative stress, autophagic-lysosomal dysfunction,mitochondrial dysfunction and prion-like spreading of misfolded proteins. Importantly, biometals and other bioelements were shown to modify these mechanisms under multiple circumstances. For example, aggregation of alpha-synuclein,a hallmark of PD and other synucleinopathies, can be enhanced by different biometals like iron, copper, aluminium and magnesium.