Unlike other human biological fluids, semen contains multiple types of amyloid fibrils in the absence of disease. These fibrils enhance HIV infection by promoting viral fusion to cellular targets, but their natural function remained unknown. The similarities shared between HIV fusion to host cell and sperm fusion to oocyte led us to examine whether these fibrils promote fertilization. Surprisingly, the fibrils inhibited fertilization by immobilizing sperm. Interestingly, however, this immobilization facilitated uptake and clearance of sperm by macrophages, which are known to infiltrate the female reproductive tract (FRT) following semen exposure. In the presence of semen fibrils, damaged and apoptotic sperm were more rapidly phagocytosed than healthy ones, suggesting that deposition of semen fibrils in the lower FRT facilitates clearance of poor-quality sperm. Our findings suggest that amyloid fibrils in semen may play a role in reproduction by participating in sperm selection and facilitating the rapid removal of sperm antigens.
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http://dx.doi.org/10.7554/eLife.24888 | DOI Listing |
Inflammopharmacology
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, ElKasr Elaini Street, Cairo, 11562, Egypt.
The currently approved drugs for Alzheimer's disease (AD) are only for symptomatic treatment in the early stages of the disease but they could not halt the neurodegeneration, additionally, the safety profile of the recently developed immunotherapy is a big issue. This review aims to explain the importance of the drugs repurposing technique and strategy to develop therapy for AD. We illustrated the biological alterations in the pathophysiology of AD including the amyloid pathology, the Tau pathology, oxidative stress, mitochondrial dysfunction, neuroinflammation, glutamate-mediated excitotoxicity, insulin signaling impairment, wingless-related integration site/β-catenin signaling, and autophagy.
View Article and Find Full Text PDFNeurochem Res
January 2025
Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Alzheimer's disease (AD) is a central nervous system degenerative disease with a stealthy onset and a progressive course characterized by memory loss, cognitive dysfunction, and abnormal psychological and behavioral symptoms. However, the pathogenesis of AD remains elusive. An increasing number of studies have shown that oligodendrocyte progenitor cells (OPCs) and oligodendroglial lineage cells (OLGs), especially OPCs and mature oligodendrocytes (OLGs), which are derived from OPCs, play important roles in the pathogenesis of AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Background: The growing number of AD patients is a public concern all over the world. During the decade, anti-amyloid beta-proteins (Aβ) monoclonal antibodies for AD patients have been developed. Among the immunotherapeutic agents, lecanemab is an anti-Aβ monoclonal antibody that binds to Aβ protofibrils (Aβ PFs), which is an intermediate molecule in Aβ species.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Michigan, Ann Arbor, MI, USA.
Background: Alzheimer's disease (AD) is the leading cause of dementia worldwide. The recent announcement that lecanemab, a monoclonal antibody targeting amyloid-b, can slow down cognitive decline in AD is a great step forward in the battle against the disease. However, the modest success achieved in the clinical trial speak to the need for developing additional pharmaceutical approaches to target other key features of AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Background: Glial cells exhibit distinct transcriptional responses to β-amyloid pathology in Alzheimer's disease (AD). While sophisticated single-cell based methods have revealed heterogeneous glial subpopulations in the human AD brain, the histological localization of these multicellular responses to AD pathology has not been fully characterized due to the loss of spatial information. Here, we combined spatial transcriptomics (ST) with immunohistochemistry to explore the molecular mechanisms in the neuritic plaque niche.
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