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Open Access 01-12-2017 | Review

Protein misfolding in neurodegenerative diseases: implications and strategies

Authors: Patrick Sweeney, Hyunsun Park, Marc Baumann, John Dunlop, Judith Frydman, Ron Kopito, Alexander McCampbell, Gabrielle Leblanc, Anjli Venkateswaran, Antti Nurmi, Robert Hodgson

Published in: Translational Neurodegeneration | Issue 1/2017

Abstract

A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network. However, there are major challenges that impact the development of novel therapies, including incomplete knowledge of druggable disease targets and their mechanism of action as well as a lack of biomarkers to monitor disease progression and therapeutic response. A notable development is the creation of collaborative ecosystems that include patients, clinicians, basic and translational researchers, foundations and regulatory agencies to promote scientific rigor and clinical data to accelerate the development of therapies that prevent, reverse or delay the progression of neurodegenerative proteinopathies.

This review is based in part on an open scientific satellite symposium entitled “Protein Misfolding – Implications and Strategies” held in conjunction with the 45^th Annual Society for Neuroscience meeting in 2015, sponsored and organized by Charles River Laboratories. The meeting panelists included: Hyunsun Park (Health & Life Science Consulting), Judith Frydman (Stanford University), John Dunlop (Astra Zeneca), Marc Baumann (University of Helsinki), Alexander McCampbell (Biogen), Ron Kopito (Stanford University), Patrick Sweeney (Royal Veterinary College, University of London, Charles River Laboratories) and Robert Hodgson (Charles River Laboratories).

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Title: Protein misfolding in neurodegenerative diseases: implications and strategies
Authors: Patrick Sweeney
Hyunsun Park
Marc Baumann
John Dunlop
Judith Frydman
Ron Kopito
Alexander McCampbell
Gabrielle Leblanc
Anjli Venkateswaran
Antti Nurmi
Robert Hodgson
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Translational Neurodegeneration / Issue 1/2017
Electronic ISSN: 2047-9158
DOI: https://doi.org/10.1186/s40035-017-0077-5

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Protein misfolding in neurodegenerative diseases: implications and strategies

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Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments

Clinical features of Parkinson’s disease with and without rapid eye movement sleep behavior disorder

Endoplasmic reticulum-mitochondria tethering in neurodegenerative diseases

The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review

Role of BACE1 in Alzheimer’s synaptic function

The role of exosomes in the pathogenesis of Alzheimer’ disease