Multipotent therapeutic probe as a potential inhibitor of amyloid aggregation in alzheimer's disease

Alzheimer's disease (AD), a progressive neurodegenerative disorder marked by amyloid-beta (Aβ) plaque deposition and cognitive decline, presents a critical challenge due to the lack of effective therapeutic and diagnostic tools. Addressing this, we report the development of multifunctional triphenylamine (TPA)-based small molecules with engineered structural and physicochemical properties tailored for targeting pathological features of AD. From a materials science perspective, these molecules exhibit a well-defined π-conjugated architecture facilitating strong π–π stacking, hydrogen bonding, and hydrophobic interactions with β-sheet-rich Aβ fibrils. Such interactions enable effective inhibition of fibril nucleation and elongation, as well as active disaggregation of preformed fibrils, as demonstrated by Thioflavin-T (ThT) assays and nanoscale morphological studies (FETEM). Moreover, the redox-active TPA scaffold imparts intrinsic antioxidant capacity, allowing for efficient scavenging of reactive oxygen species (ROS) and attenuation of oxidative-stress-induced cytotoxicity. The incorporation of metal-chelating moieties enables these molecules to sequester metal ions like Cu²? and Zn²?, thereby disrupting metal-induced Aβ aggregation and reducing redox cycling. These multifunctional molecular systems represent a new class of therapeutic materials that integrate aggregation inhibition, metal chelation, and antioxidative activity at the nanoscale. The rational design and biophysical validation of such TPA-based platforms highlight their promise for future development in nanomedicine and material-enabled strategies for combating AD.^[1,2]

[1]        P. Ghosh, K. Shokeen, S. Mondal, T. Kandasamy, S. Kumar, S. S. Ghosh, P. K.  Iyer, ACS Chem. Neurosci. 2024, 15 (2), 268–277.

[2]       P. Ghosh, P. K.  Iyer, Acc. Mater. Res. 2024, 6(1), 89–103.

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