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Age-dependent aggregation of α-synuclein in the nervous system of gut-brain axis is associated with caspase-1 activationстатья
- Авторы: Hu Q., Hong M., Huang M., Gong Q., Zhang X., Uversky V.N., Pan-Montojo F., Huang T., Zhou H., Zhu S.
- Журнал: Metabolic Brain Disease
- Том: 37
- Номер: 5
- Год издания: 2022
- Издательство: Kluwer Academic/Plenum Publishers
- Местоположение издательства: United States
- Первая страница: 1669
- Последняя страница: 1681
- Аннотация: α-Synuclein (α-Syn) plays a key role in the development of Parkinson’ desease (PD). As aging is acknowledged to be the greatest risk factor for PD, here we investigated α-Syn expression in the ileum, thoracic spinal cord, and midbrain of young (1-month-old), middle-aged (6-, 12-month-old) to old (18-month-old) mice. We demonstrated that both the levels of α-Syn monomers, oligomers and ratios of oligomers to monomers were increased with aging in the ileum, thoracic spinal cord, and midbrain. Whereas, the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, was decreased with aging in the midbrain. We failed to find corresponding α-Syn mRNA increase with aging. However, we found an increased expression of caspase-1 in the ileum, thoracic spinal cord, and midbrain. A specific caspase-1 inhibitor VX765 significantly reduced levels of both the α-Syn monomers and oligomers triggered by the rotenone in vitro. Taken together, the increase in α-Syn aggregation with aging might not occur first in the gut, but simultaneously in the nervous system of gut-brain axis. The mechanism of the age-dependent aggregation of α-Syn in nervous system is likely triggered by the aging-related caspase-1 activation.
- Добавил в систему: Уверский Владимир Николаевич