Thomas Sudhof (United States of America)
Stanford University
MCP
Thomas Christian Südhof is a neuroscientist whose work has described how neurons communicate with each other at synapses, and how such communication becomes impaired in disease. Südhof obtained his M.D. and doctoral degree in biophysics from the University of Göttingen, and trained as a postdoctoral fellow with Drs. Mike Brown and Joe Goldstein at UT Southwestern in Dallas, TX. After postdoctoral training, Südhof stayed as a faculty at UT Southwestern in Dallas, where he was the founding chair of the Department of Neuroscience. In 2008, Südhof became the Avram Goldstein Professor in the School of Medicine at Stanford University. Südhof’s research originally focused on the mechanisms by which an action potential in a presynaptic neuron triggers the secretion of neurotransmitters, which initiates synaptic transmission. This work revealed a general mechanism of regulated secretion. More recently, Südhof’s studies have centered on the question of how synapses in brain are formed and how their properties are shaped, resulting in the identification of trans-neuronal signaling mechanisms that control synaptic connections in brain. Moreover, Südhof’s work has addressed how these synaptic connections become impaired in disorders such as schizophrenia and Alzheimer’s disease, with the hope of gaining insight into possible new therapeutic avenues.

Presenter of 1 Presentation

 Conference Calendar

REGULATION OF SYNAPTIC FUNCTION BY ALZHEIMER’S ASSOCIATED GENES

Session Name
0270 - PLENARY LECTURE 1: REGULATION OF SYNAPTIC FUNCTION BY ALZHEIMER’S ASSOCIATED GENES (ID 11)
Session Type
PLENARY LECTURE
Date
Wed, 16.03.2022
Session Time
11:30 AM - 12:00 PM
Room
ONSITE PLENARY: 115-117
Lecture Time
11:30 AM - 12:00 PM
Presenter

Abstract

Abstract Body

In several neurodegenerative disorders, including Alzheimer’s Disease (AD), synapses are affected early in the disease. Multiple mutations in APP and presenilin genes cause rare cases of familial AD, while the ApoE4 variant of the ApoE gene represents the strongest genetic risk factor for AD in the general population. APP and presenilin gene mutations are thought to induce AD pathogenesis by overproducing pathogenic Abeta variants, and ApoE4 is thought to influence Abeta clearance, but how Abeta might incite AD pathogenesis and how ApoE4 might predispose to AD pathogenesis remains incompletely understood. Moreover, compelling evidence implicates microglial and possibly astrocytic dysfunction in AD pathogenesis. In my lab, we have taken a cell-biological approach to these questions with a focus on synapses because of their prominent role in AD, recognizing that synapse impairments in AD may also be secondary to microglial dysfunction. We have examined how pathogenic APP mutations, chronic impairments of presenilin function, or ApoE4 may act on synapses, using human neurons trans-differentiated from ES and iPS cells as a model. Instead of searching for potential Abeta receptors –of which there are many– or studying the effects of ApoE4 on Abeta –which still remain unclear despite decades of study– we have examined the signaling induced by pathogenic mutant forms of APP, by inhibition of presenilins, or by ApoE. Our studies suggest that APP, presenilins, and ApoE4 act directly and dramatically on synapses, albeit in a differential manner, indicating that synapses may represent a common pathway for different genetic conditions promoting AD pathogenesis.
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