Vimentin

Vimentin defined

Vimentin is a cytoskeleton protein, unique among the 70+ intermediate filament proteins because its role in structure and form is not considered its conserved role. In its first decade of research literature, no deficits — structural or otherwise -- were ever identified in pharmacological modeling when vimentin was removed (ablated via Knock Out models) that used normal conditions.

To the many biologists trying to isolate one process that critically depended on vimentin as proof of a single role conserved in evolution, this was an precedented puzzle. Eventually, when condition were altered from normal, phenotypes did emerge. Interestingly, these phenotypes were still mild until severe artificial pressures (abnormally high blood pressure, more) were applied.

This led to an understanding that vimentin exists for a role in change, and led to a third wave of exploration of disease models. Notably, disease models known for complex, multi-process disease — steep challenges requiring extensive demands on cellular processes --could not form full disease in animals that had no vimentin, indicating vimentin’s role in change was broadly essential to disease formation.

In the past decade, there has been wide realization that disease can be complex and evasive, with an array of altered cell processes that are seemingly too complex to unwind in a single target. Vimentin the facility for change provides an ideal access to block severe stages of disease where multiple features are driven by multiple components. In most Aluda indications this is 70% of the market or higher.

Vimentin in health and disease

Vimentin is an abundant cytoskeleton ‘intermediate filament’ scaffold protein with a very dynamic form. This Dynamic forms means it has a high conformational diversity that creates constantly changing binding opportunities for many proteins. Vimentin has an unusual and unique role that is conserved through evolution widely across all mammals (98%) and indeed all animals down to invertebrates (94%)—to provide adjustability to cellular processes

Binding to vimentin quantitively changes a molecular interaction that underlies a cellular activity… Similar to adding efficiency to the interaction, we call this the vimentin ‘boost’

In health, many types of cellular bind to vimentin to create an integrated, complex, responsive facility for provide protective and regenerative change.

In disease, signals escalate interact with vimentin at higher rates. Cell processes that were in normal balance, now become over-stimulated and dysregulated, creating pathology. Worse, as disease progresses, more signals of more types are involved, interact with vimentin, and this interaction drives multiple cell processes to overstimulation.

Very simple drug action

When Aluda’s compounds binds to vimentin in a specific region, the filaments can no longer have as diverse conformation which means they cannot form as many binding sites. Heightened signals driving pathology require heightened numbers of sites on vimentin to bind to and, with drug bound, there are fewer available. Normal interactions with vimentin still have enough sites. This action is:

• Specific to Disease because only the heightened pathological signals driving disease are blocked
• A breakthrough for severe disease because it creates an integrated block of complex pathology that tracks to real-time changes in the signaling that drives disease status.

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