Abstract: As the life expectancy of the world’s population increases, age-related diseases are emerging as one of the greatest problems facing modern society. The onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families. The field of aging has defined a number of interrelated pathways and cellular processes, commonly referred to as the “hallmarks of aging,” some of which have emerged as causal factors for age-related changes in brain function (López-Otín et al., 2013). Since most neurodegenerative diseases are characterized by the abnormal deposition of protein aggregates, the deregulation of proteostasis, one of the central pillars of aging, may represent one of the molecular links between normal aging and brain diseases. Indeed, a reduction in the buffering capacity of the proteostasis network is observed during normal aging in various tissues, including the brain, a phenomenon that is exacerbated in neurodegenerative diseases. One of the major nodes of the proteostasis network affected during aging in different species (humans, mice, flies, worms, and yeast) involves the function of the endoplasmic reticulum (ER) and the unfolded protein response (UPR), a signaling pathway that is activated following ER stress (Taylor and Hetz, 2020).