Abstract
Age is the common risk factor for both neurodegenerative and neuromuscular diseases. Alzheimer disease (AD), a neurodegenerative disorder, causes dementia with age progression while GNE myopathy (GNEM), a neuromuscular disorder, causes muscle degeneration and loss of muscle motor movement with age. Individuals with mutations in presenilin or amyloid precursor protein (APP) gene develop AD while mutations in GNE (UDP N-acetylglucosamine 2 epimerase/N-acetyl Mannosamine kinase), key sialic acid biosynthesis enzyme, cause GNEM. Although GNEM is characterized with degeneration of muscle cells, it is shown to have similar disease hallmarks like aggregation of Aβ and accumulation of phosphorylated tau and other misfolded proteins in muscle cell similar to AD. Similar impairment in cellular functions have been reported in both disorders such as disruption of cytoskeletal network, changes in glycosylation pattern, mitochondrial dysfunction, oxidative stress, upregulation of chaperones, unfolded protein response in ER, autophagic vacuoles, cell death, and apoptosis. Interestingly, AD and GNEM are the two diseases with similar phenotypic condition affecting neuron and muscle, respectively, resulting in entirely different pathology. This review represents a comparative outlook of AD and GNEM that could lead to target common mechanism to find a plausible therapeutic for both the diseases.
Highlights
Aging is the process, which initiates with subclinical changes at molecular level including accumulation of mutations, telomere attrition, epigenetic alterations resulting in genome instability (López-Otín et al, 2013)
While much is known for Alzheimer disease (AD), GNE myopathy (GNEM) is poorly understood rare disease
Absence of appropriate animal model system for GNEM, as UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE)−/− mice are embryonically lethal at day E8.5, restricts the understanding for genotype to phenotype co-relation
Summary
Aging is the process, which initiates with subclinical changes at molecular level including accumulation of mutations, telomere attrition, epigenetic alterations resulting in genome instability (López-Otín et al, 2013). There is a need to investigate whether hyposialylation of muscle cells, as effect of mutation in GNE, affects the glycosylation pattern and sialylation of accumulated glycoproteins and proteins like Aβ, presenilin-1 etc. Changes in the sialylation pattern of Aβ deposition cascade proteins in muscle cells may affect rimmed vacuole formation in GNEM and offer new therapeutic approach.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
