The Hebrew University of Jerusalem
The Edmond & Lily Safra Center for Brain Sciences
Hermona Soreq was trained at The Hebrew University of Jerusalem, Tel Aviv University, The Weizmann Institute of Science and the Rockefeller University. At The Hebrew University, she holds a Slesinger Chair in Molecular Neuroscience, is a founding member of the Edmond and Lily Safra Center for Brain Sciences and served as the elected Dean of the Faculty of Science from 2005-2008. Soreq pioneered and leads the application of molecular biology and genomics to the study of acetylcholine signaling, with a recent focus on the regulatory role in cholinergic signaling and the ‘changing of the guards’ concept whereby microRNAs are replaced by transfer RNA fragment controllers in states of acute need for urgent responses; and finds differences in these regulators between men and women brains. Soreq is the elected head of the International Organization of Cholinergic Mechanisms. She has authored hundreds of publications (with 58 in Science, Nature, PNAS, Neuron, EMBO Molecular Medicine and Molecular Psychiatry), was awarded Honorary PhDs in Stockholm, Erlangen and Ben Gurion University and won Teva, Rappaport and Psychoneuroimmunology prizes, the ILANIT-Katzir Prize for outstanding research achievements in the Life Sciences and the Alexander von Humboldt foundation, UC Berkeley and the Berlin NeuroCure center fellowships.

Presenter of 1 Presentation

PRE-RECORDED: Modified levels of small RNAs and their targeted Cholinergic transcripts in the Nucleus Accumbens and Hypothalamus of Alzheimer's disease brains

Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
08:30 AM - 10:30 AM
Room
ONSITE: 113
Lecture Time
10:15 AM - 10:30 AM

Abstract

Aims

The molecular pathways involved in Alzheimer’s disease (AD) pathogenesis are
incompletely understood. Several studies have identified cholinergic neuronal loss as an
early event in disease onset. To Identify possible roles of small non-coding RNAs including
microRNAs (miRs) and the recently re-discovered transfer RNA fragments (tRFs) targeting
cholinergic transcripts, we sought disease-modified levels of such RNAs carrying
complementary sequence motifs to putative cholinergic genes (as per Madrer and Soreq,
2020) in the cholinergic nucleus accumbens and the metabolism-regulating hypothalamus
of 147 AD male and female patients and 144 controls.

Methods

AD-related differences in miR and tRF levels and in their predicted cholinergic
targets were sought in small and long RNA-sequencing profiles using
statistical tests and Logistic Regression computational learning tools in brain samples from
male and female donors.

Results

Modified levels of both miRs and tRFs which target cholinergic transcripts were
found in both brain regions and enabled reliable segregation of AD patients from controls.
Examples include reduced levels in the nucleus accumbens but not the hypothalamus of
the acetylcholinesterase (AChE)-targeting miR-132, accompanying higher AChE mRNA
levels; and lower levels of a mitochondrial-genome derived Phenylalanine i-tRF in the
hypothalamus of female AD patients which correlated with elevated levels of the
high affinity choline transporter SLC5A7.

Conclusions

Our findings provide a novel approach for exploring the sex-specific AD-associated
cholinergic changes via identifying altered levels of cholinergic transcripts and
their small RNA regulators, in order to identify pathogenic pathways and possible novel
RNA-therapeutics for AD.
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