Convergent molecular defects underpin diverse neurodegenerative diseases

Journal article

In our ageing population, neurodegenerative disorders carry an enormous personal, societal and economic burden. Although neurodegenerative diseases are often thought of as clinicopathological entities, increasing evidence suggests a considerable overlap in the molecular underpinnings of their pathogenesis. Such overlapping biological processes include the handling of misfolded proteins, defective organelle trafficking, RNA processing, synaptic health and neuroinflammation. Collectively but in different proportions, these biological processes in neurons or non-neuronal cells lead to regionally distinct patterns of neuronal vulnerability and progression of pathology that could explain the disease symptomology. With the advent of patient-derived cellular models and novel genetic manipulation tools, we are now able to interrogate this commonality despite the cellular complexity of the brain in order to develop novel therapeutic strategies to prevent or arrest neurodegeneration. Here, we describe broadly these concepts and their relevance across neurodegenerative diseases.

Authors: Tofaris, G; Buckley, N

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BMJ Publishing Group
• Journal: Journal of Neurology, Neurosurgery and Psychiatry
• Volume: 89
• Issue: 9
• Pages: 962-969
• Publication date: 2018-02-19
• Acceptance date: 2018-02-01
• DOI: 10.1136/jnnp-2017-316988
• EISSN: 1468-330X
• ISSN: 0022-3050
• Pmid: 29459380
• Language: English
• Keywords: RNA metabolism; frontotemporal dementia; organelle trafficking; trinucleotide repeat disorders; parkinson’s disease; gene editing; microglia; huntington’s disease; neuroinflammation; neurodegeneration; alzheimer’s disease; iPSCs; proteostasis