Article Text

Download PDFPDF

Convergent molecular defects underpin diverse neurodegenerative diseases
  1. George K Tofaris1,
  2. Noel J Buckley2
  1. 1 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  2. 2 Department of Psychiatry, University of Oxford, Oxford, UK
  1. Correspondence to Dr George K Tofaris, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; george.tofaris{at}


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.

  • neurodegeneration
  • alzheimer’s disease
  • parkinson’s disease
  • huntington’s disease
  • frontotemporal dementia
  • trinucleotide repeat disorders
  • proteostasis
  • organelle trafficking
  • neuroinflammation
  • microglia
  • RNA metabolism
  • iPSCs
  • gene editing
View Full Text

Statistics from


  • Contributors GKT and NJB wrote the manuscript.

  • Funding GKT is funded by a Wellcome Trust Intermediate Clinical Fellowship (097479/Z/11/Z) and the Wellcome Beit Prize fellowship (097479/Z/11/A), European Union’s Horizon 2020 research and innovation programme under grant agreement no. 116060 (IMPRiND), ARUK, BMA, the Oxford Biomedical Research Centre and EPSRC (EP/M006204/1).

  • Disclaimer The opinion expressed and arguments employed herein do not necessarily reflect the official views of these funding bodies.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.