Why are neurons especially vulnerable to misfolded proteins? · Grey Matter

Most cells dilute damaged proteins by dividing, but neurons do not divide and must keep the same cell working for decades, so whatever their chaperones, proteasomes and autophagy fail to clear accumulates.

Why are neurons especially vulnerable to misfolded proteins?

Most cells dilute damaged proteins by dividing, but neurons do not divide and must keep the same cell working for decades, so whatever their chaperones, proteasomes and autophagy fail to clear accumulates. Their shape adds strain: synapses lie up to a metre from the cell body where most proteins are made, so repair and disposal depend on long-distance transport along the axon. Their energy budget is tight, and protein quality control itself consumes ATP. Aggregates of tau, amyloid beta, alpha-synuclein and other proteins that build up this way are the hallmarks of Alzheimer's, Parkinson's and related diseases.