Metals in ALS TDP-43 Pathology

International Journal of Molecular Sciences

Cecilia Ronnevi¹  Elina Berntsson²  Sebastian K. T. S. Wärmländer²  Per M. Roos³  Lassi Koski³ 

[1] Capio St. Göran Hospital, 112 19 Stockholm, Sweden;Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden;Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden;

关键词: neurodegeneration;    proteinopathy;    metallopathy;    protein aggregation;    amyloid;    metal exposure;   

DOI  :  10.3390/ijms222212193

来源: DOAJ

【 摘 要 】

Amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease and similar neurodegenerative disorders take their toll on patients, caregivers and society. A common denominator for these disorders is the accumulation of aggregated proteins in nerve cells, yet the triggers for these aggregation processes are currently unknown. In ALS, protein aggregation has been described for the SOD1, C9orf72, FUS and TDP-43 proteins. The latter is a nuclear protein normally binding to both DNA and RNA, contributing to gene expression and mRNA life cycle regulation. TDP-43 seems to have a specific role in ALS pathogenesis, and ubiquitinated and hyperphosphorylated cytoplasmic inclusions of aggregated TDP-43 are present in nerve cells in almost all sporadic ALS cases. ALS pathology appears to include metal imbalances, and environmental metal exposure is a known risk factor in ALS. However, studies on metal-to-TDP-43 interactions are scarce, even though this protein seems to have the capacity to bind to metals. This review discusses the possible role of metals in TDP-43 aggregation, with respect to ALS pathology.

【 授权许可】

Unknown