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Pathological mechanisms and therapeutic strategies for Alzheimer's disease
Ju, Yaojun; Tam, Kin
Source PublicationNeural Regeneration Research
ISSN1673-5374
2022-03-01
Abstract

Alzheimer's disease is a rather complex neurodegenerative disease, which is attributed to a combination of multiple factors. Among the many pathological pathways, synaptic dysfunctions, such as synapses loss and deficits in synaptic plasticity, were thought to be strongly associated with cognitive decline. The deficiencies in various sorts of neurotransmissions are responsible for the multifarious neurodegenerative symptoms in Alzheimer's disease, for example, the cholinergic and glutamatergic deficits for cognitive decline, the excitatory and inhibitory neurotransmission dyshomeostasis for synaptic plasticity deficits and epileptiform symptoms, and the monoamine neurotransmission for neuropsychiatric symptoms. Amyloid cascade hypothesis is the most popular pathological theory to explain Alzheimer's disease pathogenesis and attracts considerable attention. Multiple lines of genetic and pathological evidence support the predominant role of amyloid beta in Alzheimer's disease pathology. Neurofibrillary tangles assembled by microtubule-associated protein tau are other important histopathological characteristics in Alzheimer's disease brains. Cascade of tau toxicity was proved to lead to neuron damage, neuroinflammation and oxidative stress in brain. Ageing is the main risk factor of neurodegenerative diseases, and is associated with inflammation, oxidative stress, reduced metabolism, endocrine insufficiencies and organ failures. These aging related risk factors were also proved to be some of the risk factors contributing to Alzheimer's disease. In Alzheimer's disease drug development, many good therapeutic strategies have been investigated in clinical evaluations. However, complex mechanism of Alzheimer's disease and the interplay among different pathological factors call for the come out of all-powerful therapies with multiple curing functions. This review seeks to summarize some of the representative treatments targeting different pathological pathways currently under clinical evaluations. Multi-target therapies as an emerging strategy for Alzheimer's disease treatment will be highlighted.

KeywordAlzheimer's Disease Drug Development Multiple Pathologies Pathological Pathways
Language英語English
DOI10.4103/1673-5374.320970
URLView the original
Volume17
Issue3
Pages543-549
WOS IDWOS:000697690900012
WOS SubjectCell Biology ; Neurosciences
WOS Research AreaCell Biology ; Neurosciences & Neurology
Indexed BySCIE
Scopus ID2-s2.0-85112249236
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Document TypeReview article
CollectionFaculty of Health Sciences
DEPARTMENT OF PHARMACEUTICAL SCIENCES
Corresponding AuthorTam, Kin
AffiliationFaculty of Health Sciences, University of Macau, Taipa, Avenida de Universidade, Macao
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Ju, Yaojun,Tam, Kin. Pathological mechanisms and therapeutic strategies for Alzheimer's disease[J]. Neural Regeneration Research, 2022, 17(3), 543-549.
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