Wolfram syndrome (WS, MIM 222300) is a rare autosomal, recessive neurodegenerative disorder associated with mutations in WFS1, a gene that has been associated with bipolar disorder (BD).
Wolfram syndrome 1 (WS) is a rare neurodegenerative disease that is caused by mutations in the Wolfram syndrome 1 (WFS1) gene, which encodes the endoplasmic reticulum (ER) glycoprotein wolframin.
This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.
Mutations in WFS1 also cause Wolfram syndrome (WS), an autosomal recessive neurodegenerative disorder defined by diabetes mellitus, optic atrophy and often deafness, while numerous single nucleotide polymorphisms (SNPs) in WFS1 have been associated with increased risk for diabetes mellitus, psychiatric illnesses and Parkinson disease.
Here, we discuss recent updates on WIPI4's mechanistic role in autophagy and link the neuropathological manifestations of BPAN's biphasic infantile onset (epilepsy, autism) and adolescent onset (dystonic, Parkinsonism, dementia) phenotypes to neurological consequences of autophagy impairment that are now known or emerging in many other neurodevelopmental and neurodegenerative disorders.
We will systematically examine seven genes (CHN1, MDH1, PCP4, RTN1, SLC14A1, SNAP25 and VSNL1) that are altered in the three neurodegenerative diseases.
Mutation in two genes deglycase gene (DJ-1) and retromer complex component gene (VPS35) are linked with neurodegenerative disorder such as Parkinson's disease, Huntington's disease, and Alzheimer's disease.
In particular, the loss of function of VPS13A leads to chorea-acanthocytosis (ChAc), a rare neurodegenerative disease without available curative treatments.
Loss of function mutations of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) causes chorea-acanthocytosis (ChAc), a neurodegenerative disorder paralleled by deformations of erythrocytes.
The chemotactic G-protein-coupled receptor (GPCR) formyl-peptide-receptor like-1 (FPRL1) plays an essential role in the inflammatory responses of host defence mechanisms and neurodegenerative disorders such as Alzheimer's disease (AD).
Our study demonstrates a common molecular mechanism by which the activation of GPCRs leads to the suppression of autophagy and a pharmacological strategy to activate autophagy in the CNS for the treatment of neurodegenerative diseases.
Vasoactive intestinal peptide (VIP) has potent immune modulatory actions that may influence the course of neurodegenerative disorders associated with chronic inflammation.