Charlie Norwood VA Medical Center

About: Charlie Norwood VA Medical Center is a healthcare organization based out in Augusta, Georgia, United States. It is known for research contribution in the topics: Autophagy & Kidney. The organization has 349 authors who have published 490 publications receiving 16360 citations. The organization is also known as: Augusta VA Medical Center.

Moving forward with the neuromuscular junction.

Abstract: The neuromuscular junction (NMJ) is indispensable for survival. This synapse between motoneurons and skeletal muscle fibers allows posture, movement and respiration. Therefore, its dysfunction creates pathologies than can be lethal. The molecular mechanisms of NMJ development and maintenance are the subject of intensive studies. This mini-review focuses on some of the most recent discoveries. An unexpected role for a protein, rapsyn, which has been known for 40 years to aggregate acetylcholine receptors has emerged. A new cell partner at NMJ has been unmasked and is challenging our understanding of the functioning of this synapse. Toxins are now used as new tools to study degeneration/regeneration. The possibility of creating human NMJ in vitro is within reach with major consequences for drug screening. Wnts are secreted neurogenic factors that have been involved in vitro in acetylcholine receptor clustering, but their precise role in vivo remains to be clarified. All these data are raising new and exciting perspectives in the field and are discussed in this Review. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

Vps35 haploinsufficiency results in degenerative-like deficit in mouse retinal ganglion neurons and impairment of optic nerve injury-induced gliosis.

Abstract: VPS35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson’s disease (PD) and Alzheimer’s disease (AD), both neuro-degeneration disorders. However, VPS35/retromer’s function in retina or the contribution of Vps35-deficiency to retinal neuro-degenerative disorders has not been investigated. Here we provide evidence for a role of VPS35 in mouse retinal ganglion cell (RGC) survival and regeneration. VPS35 is selectively expressed in developing mouse RGCs. RGCs from young adult Vps35 heterozygotes (Vps35+/m) show degenerative-like features, such as dystrophic dendrites, reduced axon fibers, and increased TUNEL labeled RGCs. Additionally, gliosis in the optic nerve is transiently elevated in neonatal, but reduced in aged Vps35+/m mice. Optic nerve injury-induced gliosis is also attenuated in Vps35+/m mice. These results suggest that Vps35 is necessary for mouse RGC survival and regeneration, and Vps35-deficiency may contribute to the pathogenesis of retinal ganglion neuro-degeneration, a critical pathology leading to the blindness of many retinal degenerative disorders.

An Aqueous Orally Active Vaccine Targeted Against a RAGE/AB Complex as a Novel Therapeutic for Alzheimer’s Disease

Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that gradually destroys a person’s memory. Substantial evidence suggests that amyloid beta (Aβ) and the receptor for advanced glycation endproducts (RAGE) play an important and often deleterious role in the pathogenesis of AD. RAGE facilitates the translocation of Aβ from the periphery into the brain, mediates the Aβ-induced neurotoxicity, and enhances the release of pro-inflammatory cytokines increasing the inflammatory response. In addition, soluble forms of RAGE (sRAGE) and Aβ bind together in the periphery forming high molecular weight complexes that are more highly immunogenic and less neurotoxic than Aβ1-42 alone. We show here that there are elevated anti-RAGE and anti-Aβ titers (in a near 1:1 relationship) in samples analyzed from human AD patients, aged non-human primates, and AD transgenic mice (APPSWE-PS1). We show that an in vitro prepared RAGE/Aβ complex induces a greater immunogenic response (increased anti-Aβ1-42 and anti-RAGE antibody titers) in both human peripheral blood mononuclear cells (PBMCs) and immunized Balb-C mice than does either Aβ1-42 or RAGE alone. Further, pretreatment with endogenous anti-RAGE antibodies isolated from our transgenic APPSWE-PS1 mice can prevent Aβ1-42-induced neurotoxicity in cultured primary rat cortical neurons. Finally, we examine the effectiveness of an orally administered vaccine of either RAGE/Aβ complex or Aβ1-42 alone in improving cognitive function in our AD transgenic mice. Our results to date support the hypothesis that a protein complex vaccine that targets both RAGE and Aβ1-42 will provide a more effective treatment for AD than vaccination with Aβ1-42 alone.