Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations.

Article Details

Citation

Sarkar S, Rubinsztein DC

Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations.

Autophagy. 2006 Apr-Jun;2(2):132-4. Epub 2006 Apr 6.

PubMed ID
16874097 [ View in PubMed
]
Abstract

We recently showed that lithium induces autophagy via inositol monophosphatase (IMPase) inhibition, leading to free inositol depletion and reduced myo-inositol-1,4, 5-triphosphate (IP3) levels. This represents a novel way of regulating mammalian autophagy, independent of the mammalian target of rapamycin (mTOR). Induction of autophagy by lithium led to enhanced clearance of autophagy substrates, like mutant huntingtin fragments and mutant alpha-synucleins, associated with Huntington's disease (HD) and some autosomal dominant forms of Parkinson's disease (PD), respectively. Similar effects were observed with a specific IMPase inhibitor and mood-stabilizing drugs that decrease inositol levels. This may represent a new therapeutic strategy for upregulating autophagy in the treatment of neurodegenerative disorders, where the mutant protein is an autophagy substrate. In this Addendum, we review these findings, and some of the speculative possibilities they raise.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Lithium carbonateInositol monophosphatase 1ProteinHumans
Unknown
Not AvailableDetails
Lithium cationInositol monophosphatase 1ProteinHumans
Unknown
Inhibitor
Details
Lithium citrateInositol monophosphatase 1ProteinHumans
Unknown
Not AvailableDetails
Lithium succinateInositol monophosphatase 1ProteinHumans
Unknown
Not AvailableDetails