Inhibiting IGF1 Signaling Reduces Misfolded Protein Aggregation in Aging

The signaling pathways associated with insulin-like growth factor 1 (IGF-1) are one of the better studied parts of the intersection between metabolism and aging. So we might expect some marginal treatments to emerge here over the next decade, based on altering metabolism to produce modest beneficial effects by slowing the rate at which some forms of age-related damage occur. In this case the slowed damage involves build up of misfolded proteins associated with neurodegenerative conditions:

TyrNovo's novel and unique compound, named NT219, selectively inhibits the process of aging in order to protect the brain from neurodegenerative diseases, without affecting lifespan. Human neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases share two key features: they stem from toxic protein aggregation and emerge late in life.

[Researchers] discovered, working with worms, that reducing the activity of the signaling mechanism conveyed through insulin and the growth hormone IGF1, a major aging regulating pathway, constituted a defense against the aggregation of the Aβ protein which is mechanistically-linked with Alzheimer's disease. Later, [they] found that the inhibition of this signaling route also protected Alzheimer's-model mice from behavioral impairments and pathological phenomena typical to the disease. In these studies, the path was reduced through genetic manipulation, a method not applicable in humans.

[TyrNovo researchers] discovered a new set of compounds that inhibit the activity of the IGF1 signaling cascade in a unique and efficient mechanism, primarily for cancer treatment, and defined NT219 as the leading compound for further development.



Very interesting that IGF1 signaling induces protein misfolding.
I wonder if the level of misfolding in various tissues positively correlates with chronological age, or whether the rate of misfolding varies with species longevity.

It is also possible that this may be a "programmed" developmental/differentiation process. See - "Protein clumps as memory: Yeast cells are able to form a memory through an aggregate"

Posted by: Lou Pagnucco at December 5th, 2013 12:41 PM
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