Emerging links between cell competition and Alzheimer's disease

摘要

Alzheimer's disease (AD) causes a progressive loss of memory and other cognitive functions, which inexorably debilitates patients. There is still no cure for AD and effective treatments to delay or revert AD are urgently needed. On a molecular level, the excessive accumulation of amyloid-beta (A beta) peptides triggers a complex cascade of pathological events underlying neuronal death, whose details are not yet completely understood. Our laboratory recently discovered that cell competition may play a protective role against AD by eliminating less fit neurons from the brain of A beta-transgenic flies. Loss of A beta-damaged neurons through fitness comparison with healthy counterparts is beneficial for the organism, delaying cognitive decline and motor disability. In this Review, we introduce the molecular mechanisms of cell competition, including seminal works on the field and latest advances regarding genetic triggers and effectors of cell elimination. We then describe the biological relevance of competition in the nervous system and discuss how competitive interactions between neurons may arise and be exacerbated in the context of AD. Selection of neurons through fitness comparison is a promising, but still emerging, research field thatmay open newavenues for the treatment of neurological disorders.