Riqiang Yan
University of Connecticut, CT·Neuroscience
Alzheimer's disease (AD) slowly destroys memory as toxic protein clumps build up in the brain and nerve cells die. Drugs that clear these clumps have mostly disappointed, partly because they can harm healthy synapses, the connections between nerve cells.
- Fields
Neuroscience
Pharmacology
Biochemistry
- Topics
Alzheimer's disease
beta-secretase
amyloid-beta
- Grants
- 4 known grants, through Jun 2029
What they work on
- Identify potent short peptides from the CX3CL1 C-terminal domain (CX3CL1-ICD), a neuron-protecting protein region, that reduce Alzheimer's pathology and cell death in neurons and AD mouse models.
- Determine whether the N-terminal and C-terminal fragments of CX3CL1 have opposing effects on tau pathology in Alzheimer's mouse models, and how CX3CL1-ICD controls gene expression.
- Test whether deleting the amyloid-making enzyme BACE1 in microglia, the brain's immune cells, reduces tau pathology in PS19 mice, alone or combined with low-dose BACE1 inhibition in triple-transgenic AD mice.
- Test whether raising CXCL14, a chemical signal that attracts immune cells, enhances microglial migration and engulfment of plaque and tau debris, using an inducible transgenic mouse model.
- Distinguish synapse damage caused by toxic amyloid-beta from damage caused by BACE1 inhibition in mouse models, and test whether an mGluR1 positive allosteric modulator, a receptor-boosting drug, restores synaptic function.
- Determine how amyloid pathology and aging disrupt the movement of ATG9A, an autophagy protein, and drive the formation of RTN3-filled dystrophic neurites, the swollen nerve branches around plaques.
- Define how microglia contribute to the growth of dystrophic neurites around amyloid plaques in Alzheimer's brains.
More about the research
This research asks how to reduce the disease's damage while protecting or even rebuilding neurons. One line of work studies BACE1, the enzyme that starts making amyloid-beta (Aβ), the sticky peptide that forms plaques. The aim is to make blocking BACE1 safer and more effective. A second line tests protective peptides taken from a brain signaling protein. A third studies swollen, damaged nerve branches that form around plaques.
Why it matters
Alzheimer's disease affects a growing number of older people, and drugs that only target amyloid have had limited success. This work could help make BACE1-blocking drugs safer by pairing them with synapse-boosting compounds or by targeting them to glial cells. It may also yield brain-penetrating peptides that protect neurons, along with new molecular targets for preventing nerve-branch damage around plaques, with the long-term goal of preserving memory in patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jeffrey Nicholas Savas
Northwestern University, IL·Neuroscience
Build a dynamic map of how amyloid beta (Aβ) plaques form and change in the brains of aging Alzheimer's model mice, tracking distinct plaque classes and Aβ forms such as Aβ42 and Aβ38.
Tae-Wan Kim
Columbia University, NY·Neuroscience
Determine how the neuronal signal SEMA3A promotes β-amyloid uptake and a disease-associated microglia gene profile in human iPSC-derived microglia (iMGLs), independently of the TREM2 receptor.
Madepalli Lakshmana
Florida International University, FL·Neuroscience
Synthesize six sets of structurally varied TPI-132 analogs and select two with stronger activation of TFEB, a master switch for cellular recycling, plus lower toxicity and better brain penetration and solubility.
The school
University of Connecticut: 31 labs on PI Pages, $434M a year on research, 360 research doctorates a year.
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