Sho Takatori

Cryo-EM structure of pro-aggregant P301L/S320F double-mutant tau filaments formed in mouse brains following peripheral AAV delivery

Maria Kano, 木村 妙子, Haruaki Yanagisawa, Komei Yamashita et autres

Abstract Tauopathies are characterized by the accumulation of abnormally phosphorylated tau filaments, with disease-specific folds revealed by cryo-electron microscopy (cryo-EM). Here, we delivered a recombinant human tau carrying the P301L/S320F double mutation into App NL-G-F / MAPT double knock-in mice using a …

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Subtype-specific secretion of extracellular vesicles by LRRK2 and Rab GTPases under lysosomal stress

Maria Sakurai, Tomoki Kuwahara, Shoichi Suenaga, Sho Takatori et autres

LRRK2, the Parkinson's disease-associated kinase, phosphorylates a subset of Rab GTPases and regulates membrane dynamics. We previously reported that lysosomal stress activates LRRK2 and thereby induces the exocytic secretion of lysosomal contents, but the detailed secretion mechanism remained unclear. Here we found …

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Inhibition of NF-κB signaling pathway facilitates amyloid-β clearance by kallikrein-related peptidase 7

Yuki Sudo, Chia-Jen Sung, Rie Nakayoshi, Honoka Kobayashi et autres

Alzheimer disease (AD) is characterized by deposition of amyloid-β (Aβ). Decreased Aβ clearance in sporadic AD suggests that enhancing clearance is a potential therapeutic strategy. We previously identified kallikrein-related peptidase 7 (KLK7) as an astrocyte-derived Aβ-degrading protease, with reduced mRNA expression in …

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Impaired microglial TYROBP/DAP12 signaling exacerbates cortical cholinergic and noradrenergic axonal degeneration in Aβ amyloidosis

Yu Hirota, Jun Yamamoto, Sho Takatori, Yasufumi Sakakibara et autres

TREM2-TYROBP/DAP12 signaling is critical for microglial activation, and monoallelic hypofunctional TREM2 mutations aggravate amyloid-β (Aβ) pathology and increase the risk for Alzheimer’s disease (AD). In contrast, excessive microglial activation promotes synaptic loss and neurodegeneration, suggesting that the microglia exert dual roles in …

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Cryo-EM structure of pro-aggregant P301L/S320F double-mutant tau filaments formed in mouse brains following peripheral AAV delivery

Maria Kano, 木村 妙子, Haruaki Yanagisawa, Lisa Tatsumi et autres

jp (code pays fourni par la source)

Aging disrupts tissue homeostasis and constrains blastema-mediated regeneration in the Cladonema medusa

Ren Kanehisa, Hiroko Nakatani, Sho Takatori, Taisuke Tomita et autres

Abstract Regenerative capacity varies widely across animals, yet aging is often accompanied by declining tissue homeostasis and regenerative potential. In many species, regeneration of complex structures relies on epimorphic programs that form a blastema, coordinating cell proliferation and pattern reorganization after injury. …

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Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils

Hayato Etani, Sho Takatori, Wenbo Wang, Jumpei Omi et autres

BACKGROUND: Microglia play a crucial role in brain homeostasis through phagocytosis of amyloid-β (Aβ) fibrils, a hallmark of Alzheimer disease (AD) pathology. The balance between Aβ production and clearance is critical for AD pathogenesis, with impaired clearance mechanisms potentially contributing to disease …

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HAPLN2 forms aggregates and promotes microglial inflammation during brain aging in mice

Ayaka Watanabe, Shoshiro Hirayama, Itsuki Kominato, Sybille Marchese et autres

Protein aggregation is a hallmark of neurodegenerative diseases and is also observed in the brains of elderly individuals without such conditions, suggesting that aging drives the accumulation of protein aggregates. However, the comprehensive understanding of age-dependent protein aggregates involved in brain aging …

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Unraveling the complex role of microglia in Alzheimer’s disease: amyloid β metabolism and plaque formation

Sho Takatori, Taisuke Tomita

BACKGROUND: Alzheimer's disease (AD) is characterized by amyloid β (Aβ) accumulation in the brain. Recent genome-wide association studies have identified numerous AD risk genes highly expressed in microglia, highlighting their potential role in AD pathogenesis. Although microglia possess phagocytic capacity and have …

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Inhibition of NF-κB signaling pathway in astrocytes facilitates amyloid-β clearance by kallikrein-related peptidase 7

Yuki Sudo, Kazunori Kikuchi, Yung-Wen Chiu, Sho Takatori et autres

Abstract Alzheimer disease (AD) is characterized by the deposition of amyloid-β peptide (Aβ). Decreased Aβ clearance is observed in sporadic AD patients, suggesting that enhancing Aβ clearance is a potential therapeutic approach for AD. We identified kallikrein-related peptidase 7 (KLK7) as an …

jp (code pays fourni par la source)

Aggregation of HAPLN2, a component of the perinodal extracellular matrix, is a hallmark of physiological brain aging in mice

Ayaka Watanabe, Shoshiro Hirayama, Itsuki Kominato, Sybille Marchese et autres

Abstract Protein aggregation is a hallmark of neurodegenerative diseases and is also observed in the brains of elderly individuals without such conditions, suggesting that aging drives the accumulation of protein aggregates. However, the comprehensive understanding of age-dependent protein aggregates involved in brain …

jp, gb (code pays fourni par la source)

Soluble form of Lingo2, an autism spectrum disorder-associated molecule, functions as an excitatory synapse organizer in neurons

Fumiaki Yoshida, Ryota Nagatomo, Shun Utsunomiya, Misaki Kimura et autres

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired social communication and repetitive behaviors. In recent years, a pharmacological mouse model of ASD involving maternal administration of valproic acid (VPA) has become widely used. Newborn pups in this model show …

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