VAPB Aggregates and Neurodegeneration
VAP proteins are a small family of type II membrane proteins enriched on the endoplasmic reticulum that have been conserved from yeast to mammals. The N-terminal half of the proteins consists of a domain highly homologous to a polypeptide found in the motile sperm of nematodes known as the major sperm protein (MSP). A mis-sense mutation in human vapB that changes a proline residue to a serine in the most highly conserved region of the MSP domain causes a rare form of motor neuron disease, amyotrophic lateral sclerosis type 8. Whether vapB P56S is a gain or loss of function mutation is not yet clear, however, it causes the protein to aggregate and may disrupt the normal function and regulation of the ER.
KeywordsAmyotrophic Lateral Sclerosis Spinal Muscular Atrophy Amyotrophic Lateral Sclerosis Patient Motor Neuron Disease Wild Type Protein
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