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Biomedical subjects

Zeyi Wang

Publications and source records attributed to Zeyi Wang.

2 recordsLinked to original sources
PubMed2025

Targeting phagocytosis for amyloid-β clearance: implications of morphology remodeling and microglia activation probed by bifunctional chimaeras.

Amyloid-β (Aβ), a key driver of Alzheimer's disease (AD) pathogenesis, possesses diverse harmful and clearance-resistant structures that present substantial challenges to therapeutic development. Here, we demonstrate that modulating Aβ morphology, rather than Toll-like receptor 2 (TLR2)-dependent microglia activation, is essential for effective phagocytosis of Aβ species by microglia. By developing a bifunctional mechanistic probe (P2CSKn) designed to remodel Aβ and activate TLR2, we show it restructures soluble Aβ (sAβ) and fibrillar Aβ (fAβ) into less toxic hybrid aggregates (hPAβ). Critically, this structural remodeling protects microglia from Aβ toxicity while enabling robust phagocytosis. Moreover, although TLR2 activation mildly enhances Aβ uptake, it concurrently triggers detrimental inflammation that negates its benefits. Our findings establish morphological remodeling as the critical determinant of effective Aβ clearance and suggest a morphology-focused strategy for developing safe therapeutics for Aβ-related diseases.

Microglia↗
PubMed2025

The locus coeruleus influences behavior by coordinating effective integration of fear memories and sensory input.

An essential function of memory is to guide behavior for better survival and adaptation. While memory formation has been extensively studied, far less is understood about how memory retrieval influences behaviors. In the auditory Pavlovian threat conditioning paradigm using C57BL/6J mice, retrieving a conditioned threat memory is associated with spiking in two dorsomedial prefrontal cortex (dmPFC) neurons with transient (T-neurons) and sustained (S-neurons) patterns. We show here that T-neurons and S-neurons are two distinct neuronal populations with different neuronal and synaptic properties and mRNA profiles. S-neuron spiking matches freezing behavior and is required for freezing. This sustained activity in S-neurons requires auditory inputs and the release of norepinephrine (NE) in the dmPFC. The activation of the locus coeruleus (LC) is initiated by dmPFC T-neuron inputs, sustained by auditory inputs, and is required for the transition to freezing by enhancing S-neuron activity. Interestingly, LC activation precipitates a brief period during which nonconditioned cues also induce freezing. Our findings highlight the critical contribution of the LC/NE system in the transition from memory to behavior, which coordinates the effective integration of memory, sensory inputs and emotional state for optimal adaptation.

Animals↗