P2X -receptor binding in new-onset and secondary progressive MS - a [C]SMW139 PET study.

Background: PET imaging of activated microglia has improved our understanding of the pathology behind disability progression in MS, and pro-inflammatory microglia at 'smoldering' lesion rims have been implicated as drivers of disability progression. The P2X R is upregulated in the cellular membranes of activated microglia. A single-tissue dual-input model was applied to quantify P2X R binding in the normal appearing white matter, perilesional areas and thalamus among progressive MS patients, healthy controls and newly diagnosed relapsing MS patients.

Emerging TSPO-PET Radiotracers for Imaging Neuroinflammation: A Critical Analysis.

The translocator protein (TSPO) is a biomarker for imaging neuroinflammation via Positron Emission Tomography (PET) across a broad range of CNS conditions. Most clinically used PET ligands targeting TSPO have limitations, including high lipophilicity and off-target binding or poor binding to a mutated TSPO isoform present in up to 30% of the population. Research efforts over the past decade have focused on development of improved TSPO PET radiotracers that overcome these limitations.

Enhancing CNS mitophagy: drug development and disease-relevant models.

Mitophagy, the selective degradation of mitochondria, is impaired in many neurodegenerative diseases (NDs), resulting in an accumulation of dysfunctional mitochondria and neuronal damage. Although enhancing mitophagy shows promise as a therapeutic strategy, the clinical significance of mitophagy activators remains uncertain due to limited understanding and poor representation of mitophagy in the central nervous system (CNS). This review explores recent insights into which mitophagy pathways to target and the extent of modulation necessary to be therapeutic towards NDs.

Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally suppressed people with HIV.

Objectives: Virally suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used PET to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework.