Open AccessRole of Interleukin33 in Rejuvenation of Aged Neurons and Age-Related Dementias
Author(s) -
Yahuan Lou
Publication year - 2021
Publication title -
neuroscience insights
Language(s) - English
Resource type - Journals
ISSN - 2633-1055
DOI - 10.1177/26331055211030251
Subject(s) - rejuvenation , dementia , astrocyte , senescence , autophagy , downregulation and upregulation , medicine , neuroscience , neuron , oxidative stress , biology , disease , gerontology , central nervous system , gene , biochemistry , apoptosis
Late-onset Alzheimer’s disease (LOAD) is the most common age-related dementia, and its etiology remains unclear. Recent studies have linked abnormal neuronal aging to LOAD. Neurons are non-proliferative, and thus, majority of aged neurons must be rejuvenated through repairing or eliminating damaged molecules to regain their healthy status and functionalities. We discovered a surge of oxidative stress in neurons at middle age in mice. A rapid upregulation of neuronal rejuvenation is vital, while astrocyte-expressed interleukin33 (IL33), an IL1-like cytokine, is critical for this process. Thus, IL33-deficiency cripples the neuronal rejuvenation mechanisms, such as repairing DNA double strand breaks, eliminating damaged molecules by autophagy or by glymphatic drainage. IL33-deficient mice develop tau deposition and age-related dementia following a path similar to LOAD. We hypothesize that any interferences on IL33-initiated rejuvenation process for aged neurons after middle life is a potential risk for LOAD development.