Current concepts in the neuropathogenesis of mucolipidosis type IV

Lauren C. Boudewyn, Steven U. Walkley

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Mucolipidosis type IV (MLIV) is an autosomal recessive, lysosomal storage disorder causing progressively severe intellectual disability, motor and speech deficits, retinal degeneration often culminating in blindness, and systemic disease causing a shortened lifespan. MLIV results from mutations in the gene MCOLN1 encoding the transient receptor potential channel mucolipin-1. It is an ultra-rare disease and is currently known to affect just over 100 diagnosed individuals. The last decade has provided a wealth of research focused on understanding the role of the enigmatic mucolipin-1 protein in cell and brain function and how its absence causes disease. This review explores our current understanding of the mucolipin-1 protein in relation to neuropathogenesis in MLIV and describes recent findings implicating mucolipin-1′s important role in mechanistic target of rapamycin and TFEB (transcription factor EB) signaling feedback loops as well as in the function of the greater endosomal/lysosomal system. In addition to addressing the vital role of mucolipin-1 in the brain, we also report new data on the question of whether haploinsufficiency as would be anticipated in MCOLN1 heterozygotes is associated with any evidence of neuron dysfunction or disease. Greater insights into the role of mucolipin-1 in the nervous system can be expected to shed light not only on MLIV disease but also on numerous processes governing normal brain function. (Figure presented.). This article is part of the Special Issue “Lysosomal Storage Disorders”.

Original languageEnglish (US)
JournalJournal of Neurochemistry
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Mucolipidoses
Brain
Transient Receptor Potential Channels
Haploinsufficiency
Retinal Degeneration
Sirolimus
Blindness
Heterozygote
Rare Diseases
Gene encoding
Intellectual Disability
Nervous System
Neurology
Proteins
Transcription Factors
Neurons
Mutation
Feedback
Research
Genes

Keywords

  • autophagy
  • heterozygote
  • lysosomal disease
  • lysosome
  • mTOR
  • TFEB

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Current concepts in the neuropathogenesis of mucolipidosis type IV. / Boudewyn, Lauren C.; Walkley, Steven U.

In: Journal of Neurochemistry, 01.01.2018.

Research output: Contribution to journalArticle

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