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Pharmacological Adaptation of Proteostasis to Ameliorate Aging-associated Degenerative Diseases - 2023

Broad Institute via YouTube

Overview

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Explore a comprehensive seminar on chemical biology focusing on pharmacological adaptation of proteostasis to address aging-associated degenerative diseases. Delve into the cellular protein homeostasis network and its regulation of proteasome function. Learn about stress-responsive signaling pathways and their role in maintaining cellular homeostasis. Discover how small molecule kinetic stabilizers can potentially stop or slow protein homeostatic deficiencies in amyloid diseases. Examine the clinical efficacy of tafamidis in treating polyneuropathy and cardiomyopathy. Investigate high-throughput screens for drug candidates that enhance lysosomal flux and their potential to extend lifespan and healthspan. Analyze the effects of mTOR inhibitor-independent autophagy activators on clearing toxic protein aggregates in neurodegenerative diseases. Gain insights into the latest research on ameliorating tauopathies and prion-related disorders through proteostasis adaptation.

Syllabus

Introduction
Welcome
Cross beta sheet structures
Transthyroid and amyloidosis
Mutations
Dissociation
Protein Aggregation
Activation barriers
Subunit exchange
clinical trial
liver transplant
lifespan and health span
dementia
CNS phenotype
PET imaging
Brain exposure
Heart failure
Neurodegenerative diseases
Protein homeostasis network
Axon inclusions
A5 in neurons
A5 and Tau
Bloodbrain barrier
Stress response
unfolded protein response
screening strategy
prodrugs
luciferase reporter
model
trafficking index
active
conclusion
antitrypsin
Gaba receptors
Ire XP splice screen
Stress response inhibitors
Technical difficulties
Aggregation in the brain
Interallelic Trend suppressors
PDI inhibitors
Predictive principles
Viral infections

Taught by

Broad Institute

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