Neurodegerative dementias involving aberrant protein aggregation

Recently, it was shown that inclusion bodies consisting of aberrant protein aggregation are a common pathological finding in neurodegenerative dementias. It is also believed that the ubiquitin–proteasome system (UPS) is involved in these aberrant aggregations. Because the UPS is related to the unfolded protein response (UPR) in the endoplasmic reticulum (ER) through ER‐associated degradation (ERAD), we propose that the mechanism of neurodegeneration is as follows: (i) aberrant protein aggregation overloads the UPS; (ii) the disturbed UPS affects ERAD; (iii) disturbed ERAD impairs UPR; and (iv) prolonged UPR causes ER‐mediated apoptosis.