Synergistic Multi-Pronged Interactions Mediate the Effective Inhibition of Alpha-Synuclein Aggregation by the Chaperone HtrA1.

Unlabelled: The misfolding, aggregation, and the seeded spread of alpha synuclein (α-Syn) aggregates are linked to the pathogenesis of various neurodegenerative diseases, including Parkinson's disease (PD). Understanding the mechanisms by which chaperone proteins prevent the production and seeding of α-Syn aggregates is crucial for developing effective therapeutic leads for tackling neurodegenerative diseases. We show that a catalytically inactive variant of the chaperone HtrA1 (HtrA1*) effectively inhibits both α-Syn monomer aggregation and templated fibril seeding, and demonstrate that this inhibition is mediated by synergistic interactions between its PDZ and Protease domains and α-Syn.

Multifaceted interactions mediated by intrinsically disordered regions play key roles in alpha synuclein aggregation.

The aggregation of Alpha Synuclein (α-Syn) into fibrils is associated with the pathology of several neurodegenerative diseases. Pathologic aggregates of α-Syn adopt multiple fibril topologies and are known to be transferred between cells via templated seeding. Monomeric α-Syn is an intrinsically disordered protein (IDP) with amphiphilic N-terminal, hydrophobic-central, and negatively charged C-terminal domains.

Efficacy of opioids and non-opioid analgesics in the treatment of post procedure pain of burned patients: a narrative review.

Introduction: Burns are a common trauma that cause acute severe pain in up to 80% of patients. The objective of this narrative review is to evaluate the efficacy of opioids, non-steroidal anti-inflammatory drugs, paracetamol, gabapentinoids, ketamine, and lidocaine in the treatment of acute pain in burn victims.

Methodology: The databases explored were PubMed, Embase, ClinicalTrials, and OpenGrey.