Jason Weick
University of New Mexico, NM·Neuroscience
A small family of neuron-specific proteins, NSG1 and NSG2, help move other proteins to where they work in nerve cells. The lab asks two linked questions about them: do they give individual synapses (connections between neurons) their own distinct strength, and do they control a protein tied to Alzheimer's disease (AD) and frontotemporal dementia (FTD)?
- Fields
Neuroscience
Biochemistry
Biology
- Topics
Alzheimer's disease
frontotemporal dementia
Sortilin-1
- Grants
- 2 known grants, through May 2027
What they work on
- Correlate NSG1 and NSG2 levels with AD and FTD subtypes and Sortilin-1 cleavage in post-mortem human and rodent brain samples.
- Alter NSG1-2 levels in cultured human and rodent neurons to test effects on Sortilin-1 processing, trafficking, and phosphorylated Tau, TDP-43 and amyloid-beta.
- Use time-lapse and ex vivo imaging to test whether NSG1 and NSG2 are targeted to, or moved between, a distinct subset of hippocampal excitatory synapses.
- Use electrophysiology, glutamate uncaging and single and double knockout mice to test how NSG1 and NSG2 shape AMPA receptor surface levels and motor, emotional and cognitive behavior.
More about the research
The first project focuses on Sortilin-1 (SORT1), a receptor tied to late-onset AD risk and to Progranulin, a protein whose loss causes inherited FTD. SORT1 is cut into a large outer piece and a small C-terminal fragment (CTF). These fragments build up as plaque-like deposits in human AD brains but not in animal models. A protein interaction screen by the lab identified NSG1 and NSG2 as SORT1 partners. Preliminary data show NSG1 is reduced in AD and FTD patient brains, with lower NSG1 linked to more CTF. Aim 1 will compare NSG1-2 levels with disease subtype and SORT1 processing in human and rodent brain tissue. Aim 2 will change NSG1-2 levels in cultured human and rodent neurons and measure SORT1 cutting and transport, plus disease markers: phosphorylated Tau, TDP-43 and amyloid-beta.
Why it matters
Identifying how NSG proteins control Sortilin-1 processing could reveal new mechanisms behind Alzheimer's disease and frontotemporal dementia and point to possible ways to treat or prevent them. Understanding how distinct synapses get their strength adds basic knowledge of how brain networks process information during learning.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jingjing Liang
University of Arizona, AZ·Neuroscience
Test how Aggregatin, a protein encoded by the Alzheimer's-linked gene FAM222A, controls TDP-43 clumping and toxicity in neurons, using Aggregatin knockout models.
Martin Hruska
West Virginia University, WV·Neuroscience
Test how acute amyloid-beta affects PSD-95 stability in spines with different numbers of nanomodules. Use live-cell STED super-resolution imaging, with CRISPR tags on the neurons' own PSD-95 and AMPA receptors.
Charleen T Chu
University of Pittsburgh, PA·Neuroscience
Test whether loss of PINK1, a mitochondrial enzyme, impairs the transport of mitochondria into dendrites, using molecular genetic manipulations in Pink1-knockout mouse neurons and patient iPSC-derived cortical neurons.
The school
University of New Mexico: 27 labs on PI Pages, $355M a year on research, 182 research doctorates a year.
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