| dc.description.abstract | A variety of neurological diseases including Huntington’s disease (HD), Alzheimer’s disease and
Parkinson’s disease share common neuropathology, primarily featuring the presence of abnormal protein
inclusions containing specific misfolded proteins. Mutations leading to expansion of a poly-glutamine track in
Huntingtin cause HD, and trigger its misfolding and aggregation. Recent evidence indicates that alterations in
the secretory pathway, in particular the endoplasmic reticulum (ER), are emerging features of HD. Although it
is not clear how cytoplasmic/nuclear located mutant Huntingtin alters the function of the ER, several reports
indicate that mutant Huntingtin affects many essential processes related to the secretory pathway, including
inhibition of ER-associated degradation, altered ER/Golgi vesicular trafficking and axonal transport, disrupted
autophagy and abnormal ER calcium homeostasis. All these alterations are predicted to have a common
pathological outcome associated to disturbance of protein folding and maturation pathways at the ER,
generating chronic ER stress and neuronal dysfunction. Here, we review recent evidence involving ER stress
in HD pathogenesis and discuss possible therapeutic strategies to target organelle function in the context of
disease. | |
