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.