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Drug Development.
Alzheimers Dement
December 2024
Washington University School of Medicine, St. Louis, MO, USA.
Background: Alzheimer's disease neuropathology involves the deposition in brain of aggregates enriched with microtubule-binding-region (MTBR) of tau adopting an abnormal conformation between residues 306-378 in the core of aggregates. Anti-tau drugs targeting around this domain have the potential to interfere with the cell-to-cell propagation of pathological tau. Bepranemab is a humanized monoclonal Ig4 antibody binding to tau residues 235-250.
View Article and Find Full Text PDFBackground: Impaired Aβ clearance plays a key role in the common, late-onset AD. Anti-Aβ immunotherapies are controversial, in part because of high rates of serious side effects including edema, microhemorrhages, and siderosis, highlighting the importance of the development of alternative Aβ clearance strategy. Here, we introduce a bioinspired nanoparticle named MG-PE3 crossing the human blood-brain barrier (BBB) and clearing Aβ with no adverse effect.
View Article and Find Full Text PDFDrug 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 PDFDrug Development.
Alzheimers Dement
December 2024
School of Medical & Allied Sciences, K.R. Mangalam University, Gurugram, Haryana, India.
Background: Parkinson's disease is an hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid-brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Filgrastim has been reported to produce anti-oxidant, anti-inflammatory and neuromodulatory actions in previous studies.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
ADEL Institute of Science & Technology (AIST), ADEL, Inc., Seoul, Korea, Republic of (South).
Background: Abnormal aggregation and accumulation of tau is a hallmark of tauopathy including Alzheimer's disease. Effective targeting of tau for therapeutic purposes requires a clear understanding of its epitope landscape with identification of a key pathogenic tau species. Despite numerous proposed and tested tau epitopes, ranging from the N-terminus to the microtubule-binding region and C-terminus, the most effective target remains elusive.
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