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Biomedical subjects

Ai Yamamoto

Publications and source records attributed to Ai Yamamoto.

5 recordsLinked to original sources
PubMed2025

A rare genetic variant confers resistance to neurodegeneration across multiple neurological disorders by augmenting selective autophagy.

The study of disease modifiers is a powerful way to identify patho-mechanisms associated with disease. Using the strong genetic traits of Huntington's disease (HD), we identified a rare, single-nucleotide polymorphism (SNP) in WDFY3 associated with a delayed age of onset of up to 23 years. Remarkably, the introduction of the orthologous SNP into mice recapitulates this neuroprotection, significantly delaying neuropathological and behavioral dysfunction in two models of HD. The SNP increases expression of the protein autophagy-linked Fab1, YOTB, Vac1, and EEA1 (FYVE) protein (Alfy), an autophagy adaptor protein for the clearance of aggregated proteins, whose ectopic overexpression is sufficient to capture the neuroprotective effects of the variant. Increasing Alfy expression protects not only against HD but also against the toxicity due to phospho-α-synuclein and AT8-positive accumulation. By combining human and mouse genetics, we have uncovered a pathway that protects against multiple proteinopathies, revealing a much-sought-after, shared therapeutic target across a broad range of neurodegenerative diseases.

Animals↗
PubMed2006

Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway.

Conditional mouse models of polyglutamine diseases, such as Huntington's disease (HD), have revealed that cells can clear accumulated pathogenic proteins if the continuous production of the mutant transgene is halted. Invariably, the clearance of the protein leads to regression of the disease symptoms in mice. In light of these findings, it is critical to determine the pathway responsible for alleviating this protein accumulation to define targets to fight these diseases. In a functional genetic screen of HD, we found that activation of insulin receptor substrate-2, which mediates the signaling cascades of insulin and insulin-like growth factor 1, leads to a macroautophagy-mediated clearance of the accumulated proteins. The macroautophagy is triggered despite activation of Akt, mammalian target of rapamycin (mTOR), and S6 kinase, but still requires proteins previously implicated in macroautophagy, such as Beclin1 and hVps34. These findings indicate that the accumulation of mutant protein can lead to mTOR-independent macroautophagy and that lysosome-mediated degradation of accumulated protein differs from degradation under conditions of starvation.

Animals↗
PubMed2004

Sexual dimorphism of acoustic signals in the oriental white stork: non-invasive identification of sex in birds.

Identification of the sex of birds is important for captive breeding of endangered species. In the oriental white stork (Ciconia boyciana), an endangered species, both sexes produce an acoustic signal called "clatter" by rattling their mandibles together to generate sounds. We examined the structure of male and female clatter to determine whether clatter is sexually dimorphic. The acoustic structure of the clatter of the two sexes proved to be dimorphic with respect to the fundamental frequency; female clatter had higher fundamental frequencies. The fundamental frequency correlated significantly and positively with bill length, suggesting that bill morphology contributes to the sexual dimorphism of clatter. Sexing can be done by acoustic signals without capturing birds, and thus is useful as a non-invasive sexing method for ecological and conservation studies of birds.

Analysis of Variance↗
PubMed2002

Localized linear scleroderma with cutaneous calcinosis.

A 38-year-old woman developed sclerotic and atrophic changes of the left femur in the winter of 1976. In 1980, she was referred to our dermatology clinic and was diagnosed with localized linear scleroderma from the results of the physical examinations and the histological findings. Although several local and systemic treatments were employed over the following 10 years, the sclerotic lesion did not show any remarkable improvement. In 1991, several hard and white papules appeared in the lesion, and a biopsy specimen of these white papules revealed calcinosis.

Adult↗