A Fine Blur: Aging or Dementia?

Dementia is a syndrome that involves deterioration of neurons and brain damage followed by cognitive breakdown, fading control in emotion and behavior. Normal aging and dementia are not easy to distinguish, bringing difficulties in accurate diagnosis.

Misfolded Chaos and Toxic Tangles

The roots for dementia are the misfolding of tau proteins that result from their hyperphosphorylation under certain conditions. Misfolded tau proteins rapidly, autocatalytically aggregate to form tangles leading to neuron damage and drastic reduce in brain functionality.

Dissolving the Chaos

Specific clearing of aggregated proteins without disturbing the tau monomers would alleviate the difficulties. Proteasomes are factories for scavenging unwanted proteins. Decoration of aggregated proteins with small molecules mark them for proteosomal degradation. Such a process is called ‘Targeted Protein Degradation’ (TPD).

Harnessing TPD - Our Solution: AptalXero

Aptamers are artificial oligonucleotide or oligopeptide sequences that can bind to undesired aggregated proteins with very high specificity and binding affinity. We present ‘AptalXero’ that aims to use aptamers for decorating protein aggregates with small molecules like ubiquitin that can drive their fate towards degradation via the UPS System.

Motivation for Model System: Alzheimer's!

There are ma ny neurodegenerative disorders that follow dementia, but Alzheimer’s disease is the most popularly known example. Statistically, Alzheimer’s disease leads the surge in dementia occurrences.