PMID- 32864536
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211002
IS  - 2468-8673 (Electronic)
IS  - 2468-8673 (Linking)
VI  - 17
DP  - 2020 Oct
TI  - Wolfram Syndrome: a Monogenic Model to Study Diabetes Mellitus and 
      Neurodegeneration.
PG  - 115-123
LID - 10.1016/j.cophys.2020.07.009 [doi]
AB  - Wolfram syndrome (WS) is a rare, progressive disorder characterized by 
      childhood-onset diabetes mellitus, optic nerve atrophy, hearing loss, diabetes 
      insipidus, and neurodegeneration. Currently, there is no effective treatment for 
      WS, and patients typically die between 30 and 40 years of age. WS is primarily 
      caused by autosomal recessive mutations in the Wolfram syndrome 1 (WFS1) gene 
      (OMIM 222300), which encodes for wolframin (WFS1). This disorder is therefore a 
      valuable monogenic model for prevalent diseases, particularly diabetes mellitus 
      and neurodegeneration. Whereas reduced survival and secretion are known cellular 
      impairments causing WS, the underlying molecular pathways and the physiological 
      function of WFS1 remain incompletely described. Here, we characterize WFS1 as a 
      regulator of intracellular calcium homeostasis, review our current understanding 
      of the disease mechanism of WS, and discuss candidate treatment approaches. These 
      insights will facilitate identification of new therapeutic strategies not only 
      for WS but also for diabetes mellitus and neurodegeneration.
FAU - Fischer, Tom T
AU  - Fischer TT
AUID- ORCID: 0000-0002-2138-9102
AD  - Department of Pharmacology, Yale University, New Haven, CT-06520, USA.
AD  - Institute of Pharmacology, University of Heidelberg, Germany.
FAU - Ehrlich, Barbara E
AU  - Ehrlich BE
AUID- ORCID: 0000-0001-9657-9704
AD  - Department of Pharmacology, Yale University, New Haven, CT-06520, USA.
AD  - Department of Molecular Physiology, Yale University, New Haven, CT-06520, USA.
LA  - eng
GR  - P01 DK057751/DK/NIDDK NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20200715
PL  - England
TA  - Curr Opin Physiol
JT  - Current opinion in physiology
JID - 101715200
PMC - PMC7451204
MID - NIHMS1612505
OTO - NOTNLM
OT  - Orphan disease
OT  - WFS1
OT  - ibudilast
OT  - intracellular calcium signaling
OT  - neurodevelopment
OT  - pancreatic beta-cells
COIS- Competing interests B.E.E is a founder of Osmol Therapeutics, a company that is 
      targeting NCS1 for therapeutic purposes.
EDAT- 2020/08/31 06:00
MHDA- 2020/08/31 06:01
PMCR- 2021/10/01
CRDT- 2020/09/01 06:00
PHST- 2020/09/01 06:00 [entrez]
PHST- 2020/08/31 06:00 [pubmed]
PHST- 2020/08/31 06:01 [medline]
PHST- 2021/10/01 00:00 [pmc-release]
AID - 10.1016/j.cophys.2020.07.009 [doi]
PST - ppublish
SO  - Curr Opin Physiol. 2020 Oct;17:115-123. doi: 10.1016/j.cophys.2020.07.009. Epub 
      2020 Jul 15.