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Drug Development.
Alzheimers Dement
December 2024
ADEL Institute of Science & Technology (AIST), ADEL, Inc., Seoul, Korea, Republic of (South).
Background: The Apolipoprotein E4 isoform (ApoE4), encoded by the APOE gene, stands out as the most influential genetic factor in late-onset Alzheimer's disease (LOAD). The ApoE4 isoform contributes to metabolic and neuropathological abnormalities during brain aging, with a strong correlation observed in APOE4-positive Alzheimer's disease cases between phosphorylated tau burden and amyloid deposition. Despite compelling evidence of APOE-mediated neuroinflammation influencing the progression of tau-mediated neurodegeneration, the molecular mechanisms underlying these phenomena remain largely unknown.
View Article and Find Full Text PDFBackground: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFBackground: Rater change is inevitable in often lengthy clinical trials in Alzheimer's disease. Other groups have previously assessed the impact of rater change on data variability. Their conclusions varied, possibly due to differing methodologies (e.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a neurodegenerative disorder without a cure. Targeting this multifactorial disease by repurposing FDA approved drugs serves as a faster mode of treatment due to its pre-established human safety. We tested terazosin (TZ), an a-1 adrenergic receptor (AR) antagonist and phosphoglycerate kinase-1 (PGK1) activator as having potential to treat AD.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Shoolini University, Solan, Himachal Pradesh, India.
Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline, neuroinflammation, and mitochondrial dysfunction. In Alzheimer's, abnormal Mitochondrial Permeability Transition Pore (mPTP) activity may contribute to mitochondrial dysfunction and neuronal damage. Withanolide A, a naturally occurring compound derived from Withania somnifera, have shown potential neuroprotective effects in various neurological disorders.
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