Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential.
Lina GaoYun ZhangKeenan SterlingWeihong SongPublished in: Translational neurodegeneration (2022)
Synaptic abnormalities are a cardinal feature of Alzheimer's disease (AD) that are known to arise as the disease progresses. A growing body of evidence suggests that pathological alterations to neuronal circuits and synapses may provide a mechanistic link between amyloid β (Aβ) and tau pathology and thus may serve as an obligatory relay of the cognitive impairment in AD. Brain-derived neurotrophic factors (BDNFs) play an important role in maintaining synaptic plasticity in learning and memory. Considering AD as a synaptic disorder, BDNF has attracted increasing attention as a potential diagnostic biomarker and a therapeutical molecule for AD. Although depletion of BDNF has been linked with Aβ accumulation, tau phosphorylation, neuroinflammation and neuronal apoptosis, the exact mechanisms underlying the effect of impaired BDNF signaling on AD are still unknown. Here, we present an overview of how BDNF genomic structure is connected to factors that regulate BDNF signaling. We then discuss the role of BDNF in AD and the potential of BDNF-targeting therapeutics for AD.
Keyphrases
- stress induced
- cognitive impairment
- cerebral ischemia
- traumatic brain injury
- small molecule
- oxidative stress
- gene expression
- machine learning
- working memory
- cognitive decline
- human health
- risk assessment
- endoplasmic reticulum stress
- multiple sclerosis
- copy number
- lps induced
- deep learning
- molecular dynamics
- dna methylation
- brain injury
- cell proliferation
- lipopolysaccharide induced
- cell cycle arrest
- subarachnoid hemorrhage
- signaling pathway
- genome wide