Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials.

Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aß production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.

A dielectric-modulated field-effect transistor for biosensing.

Interest in biosensors based on field-effect transistors (FETs), where an electrically operated gate controls the flow of charge through a semiconducting channel, is driven by the prospect of integrating biodetection capabilities into existing semiconductor technology. In a number of proposed FET biosensors, surface interactions with biomolecules in solution affect the operation of the gate or the channel. However, these devices often have limited sensitivity. We show here that a FET biosensor with a vertical gap is sensitive to the specific binding of streptavidin to biotin. The binding of the streptavidin changes the dielectric constant (and capacitance) of the gate, resulting in a large shift in the threshold voltage for operating the FET. The vertical gap is fabricated using simple thin-film deposition and wet-etching techniques. This may be an advantage over planar nanogap FETs, which require lithographic processing. We believe that the dielectric-modulated FET (DMFET) provides a useful approach towards biomolecular detection that could be extended to a number of other systems.