Abstract
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia among aged people whose population is rapidly increasing. AD not only seriously affects the patient’s physical health and quality of life, but also adds a heavy burden to the patient’s family and society. It is urgent to understand AD pathogenesis and develop the means of prevention and treatment. AD is a chronic devastating neurodegenerative disease without effective treatment. Current approaches for management focus on helping patients relieve or delay the symptoms of cognitive dysfunction. The calcium ion (Ca2+) is an important second messenger in the function and structure of nerve cell circuits in the brain such as neuronal growth, exocytosis, as well as in synaptic and cognitive function. Increasing numbers of studies suggested that disruption of intracellular Ca2+ homeostasis, especially the abnormal and excessive Ca2+ release from the endoplasmic reticulum (ER) via the ryanodine receptor (RYR), plays important roles in orchestrating the dynamic of the neuropathology of AD and associated memory loss, cognitive dysfunction. Dantrolene, a known antagonist of the RYR and a clinically available drug to treat malignant hyperthermia, can ameliorate the abnormal Ca2+ release from the RYR in AD and the subsequent pathogenesis, such as increased β-secretase and γ-secretase activities, production of Amyloid-β 42 (Aβ 42) and its oligomer, impaired autophagy, synapse dysfunction, and memory loss. However, more studies are needed to confirm the efficacy and safety repurposing dantrolene as a therapeutic drug in AD.
Highlights
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia among aged people [1,2]
In the US alone, an estimated 5.5 million patients are diagnosed with AD, a devastating neurodegenerative disease without effective treatment [4,7]
Recent studies suggested that mutated PS2 or amyloid precursor protein (APP) contributed to the calcium dysregulation and pathogenesis of AD by over activation of RYR37 [104,108,109,110]
Summary
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia among aged people [1,2]. Because Tau pathology play important roles in neurodegeneration, which is usually seen together with amyloid pathology, researchers tried to develop new drugs targeting hyperphosphorylated NFT [22,25]. A number of studies have shown that disruption of intracellular Ca2+ homeostasis plays important roles in orchestrating dynamic of the neuropathology of AD and associated memory loss, cognitive dysfunction [36,37,38,39,40,41].
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