Autophagy–lysosomal-associated neuronal death in neurodegenerative disease

Nixon, Ralph A.

doi:10.1007/s00401-024-02799-7

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2024

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Cited by 4 publications

References 251 publications

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Regulated cell death in neurodegeneration: pathways and therapeutic horizons

Thal,

De Strooper

2024

Acta Neuropathol

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Regulated cell death in neurodegeneration: pathways and therapeutic horizons

Thal,

De Strooper

2024

Acta Neuropathol

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Pathological axonal enlargement in connection with amyloidosis, lysosome destabilization and hemorrhage is a major defect in Alzheimer’s disease

Fu,

Li,

Zhang

et al. 2024

Preprint

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Alzheimer’s disease (AD) is a multi-amyloidosis disease with Aβ deposits in the cerebral blood vessels, microaneurysms and senile plaques. How Aβ amyloidosis affects axon pathology is not well-examined. We studied the Aβ-related axonal phenotypes in the AD brains with histochemistry, immunohistochemistry and fluorescence imaging. We found that widespread axonal amyloidosis existed in the AD brain tissues with a distinct axonal enlargement phenotype. Aβ-positive axon diameters in AD brain tissues were 1.72 times as large as control brain axons by average and they showed a significant loss of axonal structural protein MAP2. Axonal amyloidosis was also associated with Tau phosphorylation and lysosome destabilization. In addition, axonal amyloidosis bore the markers of hemorrhagic insults such as ApoE, HBA, HbA1C, and Hemin. Under extreme conditions, axon breakage was observed, which likely results in Wallerian degeneration in some axons. We believe that axonal amyloidosis and enlargement associated with chronic microhemorrhage and lysosome destabilization is a major neurological defect in the Alzheimer’s disease.

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Editorial: The (un)desirability of cell death in health and disease: emerging modulators and their mechanisms

Barbosa,

Souza-Fagundes

et al. 2024

Front. Cell Dev. Biol.

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Autophagy–lysosomal-associated neuronal death in neurodegenerative disease

Cited by 4 publications

References 251 publications

Regulated cell death in neurodegeneration: pathways and therapeutic horizons

Regulated cell death in neurodegeneration: pathways and therapeutic horizons

Pathological axonal enlargement in connection with amyloidosis, lysosome destabilization and hemorrhage is a major defect in Alzheimer’s disease

Editorial: The (un)desirability of cell death in health and disease: emerging modulators and their mechanisms

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