Life Sciences & Biotechnology
Title : | Real-time evaluation of spatio-temporal fingerprints of nanomachinery involved in the early onset of Alzheimer's Disease at an excitatory synapse |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Neuroscience, Nanotechnology |
Principal Investigator : | Prof. Deepak Kumaran Nair, Indian Institute Of Science, Bangalore, Karnataka |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | deepak@iisc.ac.in |
Details
Executive Summary : | Alzheimer's disease (AD) is characterized by the accumulation and deposition of β-amyloid peptide and hyperphosphorylated tau protein, leading to senile plaques and neurofibrillary tangles. Research in Aβ fibrils has shown that both monomeric and multimeric forms of Aβ target synapses, disrupting synaptic signaling mechanisms. However, there is limited understanding of the role of full-length Amyloid Precursor Protein (APP), a precursor to Aβ, and its role towards basal synaptic function. The selective interaction of APP to different secretases is crucial for producing Aβ fragments. Recent findings from Deepak Nair's laboratory indicate that around 10,000 APP molecules are present at the synaptic membrane, and their processing machinery is clustered into functional domains of 100nm. This suggests a strong overlap between the machinery involved in processing APP and synaptic transmission machinery involved in localization and recruitment of glutamatergic receptors to the synapse. Detrimental modifications in APP may directly influence synaptic organization or alter the composition, affecting the basal signatures of synaptic transmission and plasticity. Perturbations of synapses during AD are correlated with decline and memory impairment in the early stages. Failure in glutamatergic receptor regulatory processes involved in excitatory synaptic transmission and plasticity is critical for these changes resulting in synaptic perturbations. Exploring the role of APP, its detrimental/protective genetic variants, and its proteolytic products in influencing molecular organization and regulation of synaptic transmission in an excitatory synapse will be key to understanding fundamental mechanisms leading to synaptic dysfunction during the early onset of AD. |
Co-PI: | Prof. Balaji Jayaprakash, Indian Institute Of Science, Bangalore, Karnataka-560012 |
Total Budget (INR): | 66,63,888 |
Organizations involved