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Abnormal Protein Aggregation
- Molecular classification
- Pathological Process
01
Overview
Abnormal protein aggregation refers to the process by which proteins misfold and accumulate into insoluble aggregates or inclusions within cells or tissues. This phenomenon is a defining pathological feature of many neurodegenerative diseases. Aggregated proteins disrupt normal cell function through various mechanisms such as impairing proteostasis networks, overwhelming degradation systems (UPS/ALP), inducing oxidative stress, disrupting organelles like mitochondria or endoplasmic reticulum, interfering with synaptic transmission in neurons, and triggering apoptosis. Because abnormal protein aggregation is central to the pathogenesis of numerous neurodegenerative disorders it has become an attractive target for therapeutic intervention.
02
Mechanism of action
Inhibition of aggregation, enhancement of cellular clearance, modulation of chaperones
03
Biological functions
Protein misfoldingOligomerizationFibril formationInclusion body formationDisruption of proteostasisImpairment of degradation pathways (UPS/ALP)Induction of oxidative stressOrganelle disruption (mitochondria, ER)Interference with synaptic transmissionApoptosis
04
Disease associations
Alzheimer’s diseaseParkinson’s diseaseHuntington’s diseaseAmyotrophic lateral sclerosis (ALS)Prion diseases
05
Safety considerations
Off-target effects of aggregation inhibitorsDisruption of normal protein foldingImmune response to aggregated proteinsDifficulty in targeting specific aggregatesDelivery of therapeutics across the blood-brain barrier
06
Biomarkers
Amyloid-beta (Aβ) levelsTau protein levelsAlpha-synuclein levelsHuntingtin protein levelsSOD1 levelsPrion protein levels
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