Details

Autor(en) / Beteiligte

• Gao, Ju
• Wang, Luwen
• Yan, Tingxiang
• Perry, George
• Wang, Xinglong

Titel

TDP-43 proteinopathy and mitochondrial abnormalities in neurodegeneration

Ist Teil von

• Molecular and cellular neuroscience, 2019-10, Vol.100, p.103396-103396, Article 103396

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

ScienceDirect

Beschreibungen/Notizen

• Genetic mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Importantly, TDP-43 proteinopathy, characterized by aberrant phosphorylation, ubiquitination, cleavage or nuclear depletion of TDP-43 in neurons and glial cells, is a common prominent pathological feature of various major neurodegenerative diseases including ALS, FTD, and Alzheimer's disease (AD). Although the pathomechanisms underlying TDP-43 proteinopathy remain elusive, pathologically relevant TDP-43 has been repeatedly shown to be present in either the inside or outside of mitochondria, and functionally involved in the regulation of mitochondrial morphology, trafficking, and function, suggesting mitochondria as likely targets of TDP-43 proteinopathy. In this review, we first describe the current knowledge of the association of TDP-43 with mitochondria. We then review in detail multiple mitochondrial pathways perturbed by pathological TDP-43, including mitochondrial fission and fusion dynamics, mitochondrial trafficking, bioenergetics, and mitochondrial quality control. Lastly, we briefly discuss how the study of TDP-43 proteinopathy and mitochondrial abnormalities may provide new avenues for neurodegeneration therapeutics. •This review describes our current knowledge of the physical association of TDP-43 with mitochondria.•This review describes our current knowledge of mitochondrial pathways perturbed by pathological TDP-43.•This review describes our perspective of TDP-43 targeted therapeutic approaches.