Daniel M. Michaelson (Israel)
Tel Aviv University
Department Neurobiology
Daniel M. Michaelson is Professor of Neurobiology at the Faculty of Life Sciences at Tel Aviv University. He graduated from the Hebrew university in Jerusalem with a BSc in Physics and mathematics in 1968 and obtained in PhD in Biophysics form the University of California Berekely in 1973 . His post doctoral training was in neurochemistry at the labortatory of Professor M.A. Raftery at the California Institute of Technology where he studied the nictonic acetylcholine receptors and it's functional reconstitution He joined the faculty of life science at Tel Aviv university in 1974 where his research first focused on the mechanisms underlying neurotransmitter release. His current research focuses on Alzheimer's disease and the mechanisms underlying the effects of genetic risk factors of the disease and their crosstalk with environmental factors . Specifically the research focuses on apolipoprotein E4, which is the most prevalent gentic risk factor of Alzheimers disease, and on the development of therapeutic approaches to counteract its pathological effects.

Moderator of 1 Session

 Conference Calendar
SYMPOSIUM

APOE MECHANISMS AND TREATMENT STRATEGIES 2

Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE: 114
Chair(s)

Presenter of 1 Presentation

 Conference Calendar

APOE4: AN EMERGING THERAPEUTIC TARGET FOR ALZHEIMER’S DISEASE

Session Name
0740 - APOE: MECHANISMS AND TREATMENT STRATEGIES 1 (ID 37)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 112
Lecture Time
04:30 PM - 04:45 PM
Presenter

Abstract

Abstract Body

Objectives: The overall objective of this study was to develop a low molecular weight and brain permeable druggable ABCA1 activator that can reverse the hypo-lipidation of apoE4 and the associated brain pathological effects.

Methods: High-ThroughputScreening (HTS) was first performed utilizing a cellular cholesterol efflux assay which was based on measurements of hit derived and ABCA1 driven increased lipidation of apoE4 as well as on assessment of the size of the lipidated particle utilizing fluorescence polarization measurements .Potential hits were then subjected to an orthogonal assay (i.e. digestion of senile plaques) in order to assess the extent to which the hits can reverse an efflux-independent apoE4 driven phenotype.

Results: Analysis of the HTS ,plaque digestion, and ABCA1 target recognition results led to the discovery of a lead compound which reacted optimally in theses assays, Further mechanistic studies revelled that the decreased levels of apoE and growth factor receptors which are induced by apoE4 in primary neuronal cultures are reversed by the lead compound. Preliminary in vivo studies revealed that injection of the lead compound into the brains of the apoE4 TR mice with Alzet mini osmotic pumps reversed the hypo-lipidation of apoE4 and increased the brain levels of apoE4

Conclusions: The results obtained show that the pathological effects of apoE4 can be reduced by reversal of the hypolipidation of apoE4 and suggest a novel approach for the treatment of the pathological effects of apoE4 in AD

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