Skip to main content

Filter Search Results

Publication Year

Animal Models

Topic Area

Methods

Funding Mechanism

Division of Comparative Medicine

Collaborating ICs

Selected Grantee Publications

Mechanical Force of Uterine Occupation Enables Large Vesicle Extrusion From Proteostressed Maternal Neurons

Wang et al., eLife. 2024.

https://pubmed.ncbi.nlm.nih.gov/39255003

This study investigates how mechanical forces from uterine occupation influence large vesicle extrusion (exopher production) from proteostressed maternal neurons in Caenorhabditis elegans. Exophers, previously found to remove damaged cellular components, are poorly understood. Researchers demonstrate that mechanical stress significantly increases exopher release from touch receptor neurons (i.e., ALMR) during peak reproductive periods, coinciding with egg production. Genetic disruptions reducing reproductive activity suppress exopher extrusion, whereas interventions promoting egg retention enhance it. These findings reveal that reproductive and mechanical factors modulate neuronal stress responses, providing insight on how systemic physiological changes affect neuronal health and proteostasis, with broader implications for reproductive-neuronal interactions. Supported by ORIP (R24OD010943, P40OD010440), NIA, and NIGMS.

Innate Immunity Stimulation via CpG Oligodeoxynucleotides Ameliorates Alzheimer’s Disease Pathology in Aged Squirrel Monkeys

Patel et al., Brain: A Journal of Neurology. 2021.

https://pubmed.ncbi.nlm.nih.gov/34128045/

Alzheimer's disease is the only illness among the top 10 causes of death for which there is no disease-modifying therapy. The authors have shown in transgenic Alzheimer's disease mouse models that harnessing innate immunity via TLR9 agonist CpG oligodeoxynucleotides (ODNs) modulates age-related defects associated with immune cells and safely reduces amyloid plaques, oligomeric amyloid-β, tau pathology, and cerebral amyloid angiopathy (CAA). They used a nonhuman primate model for sporadic Alzheimer's disease pathology that develops extensive CAA-elderly squirrel monkeys. They demonstrate that long-term use of Class B CpG ODN 2006 induces a favorable degree of innate immunity stimulation. CpG ODN 2006 has been well established in numerous human trials for a variety of diseases. This evidence together with their earlier research validates the beneficial therapeutic outcomes and safety of this innovative immunomodulatory approach. Supported by ORIP (P40OD010938), NINDS, NIA, and NCI.