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Review
. 2023 Feb 16;186(4):693-714.
doi: 10.1016/j.cell.2022.12.032.

Hallmarks of neurodegenerative diseases

David M Wilson 3rd  1 , Mark R Cookson  2 , Ludo Van Den Bosch  3 , Henrik Zetterberg  4 , David M Holtzman  5 , Ilse Dewachter  6
Affiliations
Free article
Review

Hallmarks of neurodegenerative diseases

David M Wilson 3rd et al. Cell. .
Free article

Abstract

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks of NDD: pathological protein aggregation, synaptic and neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. We describe the hallmarks, their biomarkers, and their interactions as a framework to study NDDs using a holistic approach. The framework can serve as a basis for defining pathogenic mechanisms, categorizing different NDDs based on their primary hallmarks, stratifying patients within a specific NDD, and designing multi-targeted, personalized therapies to effectively halt NDDs.

Keywords: DNA and RNA defects; cytoskeletal defects; energy homeostasis; hallmarks; inflammation; neurodegeneration; neurodegenerative disease; protein aggregation; proteostasis; synaptic and neuronal network dysfunction.

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Conflict of interest statement

Declaration of interests D.M.H. is a co-founder with equity in C2N Diagnostics. He consults for C2N Diagnostics, Genentech, Denali, Cajal Neurosciences, and Alector. H.Z. has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Passage Bio, Pinteon Therapeutics, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). L.V.D.B. is head of the Scientific Advisory Board of Augustine Therapeutics (Leuven, Belgium) and is part of the Investment Advisory Board of Droia Ventures (Meise, Belgium). L.V.D.B. has a patent on the use of HDAC inhibitors to treat CMT disease (Serial No. 61/404,796).

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