Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease.
Neurofibrillary tangles (aggregates of cytoskeletal Tau protein) and senile plaques (aggregates mainly formed by amyloid β peptide) are two landmark lesions in Alzheimer׳s disease. Some researchers have proposed tangles, whereas others have proposed plaques, as primary lesions. For a long time, these were thought of as independent mechanisms. However, experimental evidence suggests that both lesions are intimately related. We review here some molecular pathways linking amyloid β and Tau toxicities involving, among others, glycogen synthase kinase 3β, p38, Pin1, cyclin-dependent kinase 5, and regulator of calcineurin 1. Understanding amyloid β and Tau toxicities as part of a common pathophysiological mechanism may help to find molecular targets to prevent or even treat the disease.
Department of Physiology, Faculty of Medicine, University of Valencia and Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, 46010 Valencia, Spain.
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A
Lloret
Department of Physiology, Faculty of Medicine, University of Valencia and Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, 46010 Valencia, Spain.
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Fuchsberger
Department of Physiology, Faculty of Medicine, University of Valencia and Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, 46010 Valencia, Spain.
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Giraldo
Department of Physiology, Faculty of Medicine, University of Valencia and Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, 46010 Valencia, Spain. Electronic address: jose.vina@uv.es.
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Viña
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D006801:Humans; D010766:Phosphorylation; D066263:Protein Aggregation, Pathological / Q000209:etiology* / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016875:tau Proteins
Alzheimer׳s disease; Amyloid β; Dementia; Free radicals; Neurodegeneration; p-Tau