Skip to main content

Targeting Tau-induced cognitive decline with antisense oligonucleotides to synaptogyrin-3

Objective

Tauopathies (that include Alzheimer’s disease) are characterized by hyperphosphorylation or mutations in the microtubuleassociated protein Tau. This reduces the affinity of Tau to bind microtubules and increases the levels of soluble detached Tau in neurons. Previous ERC-supported work from my lab showed that pathogenic Tau accumulates at pre-synaptic terminals and clusters synaptic vesicles in mouse and fly Tauopathy models and in Alzheimer patient brain samples. This pre-synaptic Tau reduces vesicle mobility and neurotransmitter release (Zhou et al., 2017). The interaction of Tau with synaptic vesicles occurs via the synaptic vesicle-associated protein Synaptogyrin-3. Lowering the levels of Synaptogyrin-3 blocks the ability of Tau to efficiently bind to synaptic vesicles (McInnes et al., 2018). Hence, Synaptogyrin-3 is a promising therapeutic target to tackle tauopathies. In this project I propose to use antisense oligonucleotides (ASOs) to reduce the levels of Synaptogyrin-3 in the brain of Tauopathy mouse models to rescue tau-induced pre-synaptic defects, including cognitive decline. ASO-technology has vastly improved over the past years and was recently approved to treat other degenerative disorders. My goal is to provide in vivo proof-of-concept that targeting Synaptogyrin-3 with an ASO in a therapeutic setting suppresses Tau-induced defects, including cognitive decline.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/basic medicine/neurology/alzheimer

Call for proposal

ERC-2020-PoC
See other projects for this call

Funding Scheme

ERC-POC-LS - ERC Proof of Concept Lump Sum Pilot

Host institution

VIB VZW
Address
Rijvisschestraat 120
9052 Zwijnaarde - Gent
Belgium
Activity type
Research Organisations
EU contribution
€ 150 000

Beneficiaries (1)

VIB VZW
Belgium
EU contribution
€ 150 000
Address
Rijvisschestraat 120
9052 Zwijnaarde - Gent
Activity type
Research Organisations