Abstract
Alzheimer’s disease (AD) is the most common form of dementia in the elderly, which is characterized by progressive cognitive impairment. Neuritic plaques, neurofibrillary tangles and neuronal loss are the major neuropathological hallmarks in AD brains. TMP21 is a key molecule for protein trafficking in cells. Growing evidence indicates that TMP21 is dysregulated in AD, which plays a pivotal role in neuritic plaque formation. Therefore, we aim to review the dysregulation of TMP21 in AD, the role of TMP21 in neuritic plaque formation and underlying mechanisms. Moreover, the potential role of TMP21 in neurofibrillary tangle formation, synaptic impairment and neuronal loss is discussed. It will provide an outlook into the potential of regulating TMP21 as a therapeutic approach for AD treatment.
Highlights
Alzheimer’s disease (AD) is the most common form of neurodegenerative disorders leading to dementia in the elderly
TMP21 regulates γ-secretase cleavage of APP at the γ-site, it has no effect on the γ-secretase cleavage of Notch at the ε-site (Chen et al, 2006; Bromley-Brits and Song, 2012)
TMP21 dysregulation might contribute to synaptic impairment and neuronal loss, which is mediated by the direct effect of TMP21 dysregulation or the indirect effect of TMP21 dysregulation-induced increased Amyloid β-protein (Aβ) generation and Tau phosphorylation
Summary
Alzheimer’s disease (AD) is the most common form of dementia in the elderly, which is characterized by progressive cognitive impairment. Neurofibrillary tangles and neuronal loss are the major neuropathological hallmarks in AD brains. TMP21 is a key molecule for protein trafficking in cells. Growing evidence indicates that TMP21 is dysregulated in AD, which plays a pivotal role in neuritic plaque formation. We aim to review the dysregulation of TMP21 in AD, the role of TMP21 in neuritic plaque formation and underlying mechanisms. The potential role of TMP21 in neurofibrillary tangle formation, synaptic impairment and neuronal loss is discussed. It will provide an outlook into the potential of regulating TMP21 as a therapeutic approach for AD treatment
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