Age-Related Diseases in African Turquoise Killifish
We have developed various Parkinson's disease models using medaka and zebrafish
through drug administration and genetic modification. These models have
contributed to our understanding of Parkinson's disease pathology. However,
creating animal models that mimic sporadic Parkinson's disease, which constitutes
the majority of cases, remains challenging.
Fish offer several advantages, one of which is their incredible diversity.
In Mozambique, Africa, there are puddles that form only during the short
rainy season and dry up during the dry season. Fish inhabit these puddles
only during the rainy season. Regardless of their potential longevity,
they die when the water dries up. They survive as a species by laying drought-resistant
eggs in the soil, which hatch in the rainy season. Consequently, longevity
traits are not selected for, making them among the shortest-lived vertebrates.
We hypothesized that age-dependent diseases, such as Parkinson's disease,
become more likely with aging as an underlying factor. By analyzing the
African turquoise killifish, we discovered that aging alone led to phenotypes
similar to human Parkinson's disease, such as dopaminergic neuron degeneration
and α-synuclein accumulation. This finding was reported in Cell Reports
in 2019 (Matsui et al., Cell Rep., 2019). Further detailed analysis of
α-synuclein post-translational modifications in the brains of both these
fish and humans identified T64 phosphorylation, which is associated with
α-synuclein neurotoxicity in Parkinson's disease. This phosphorylation
was found to disrupt α-synuclein oligomer formation and induce toxicity,
as reported in PNAS (Matsui et al., Proc. Natl. Acad. Sci. USA, 2023, Press release: https://www.bri.niigata-u.ac.jp/research/result/20230601_matsui_pressrelease.pdf)。
Currently, we are conducting pathological and various omics analyses of aging and age-related diseases in the African turquoise killifish to provide new insights into aging and age-related diseases in humans and other life forms.