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Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
Protein Folding01:25

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...

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Related Experiment Video

Updated: May 13, 2026

Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis
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Recent developments in targeting protein misfolding diseases.

Rajiah Aldrin Denny1, Lori Krim Gavrin, Eddine Saiah

  • 1BioTherapeutics Chemistry, Pfizer Worldwide Medicinal Chemistry, 200 CambridgePark Drive, Cambridge, MA 02140, USA.

Bioorganic & Medicinal Chemistry Letters
|March 5, 2013
PubMed
Summary

Small molecules are emerging as key therapeutics for protein misfolding diseases. This review covers small molecules that modulate protein folding, stabilization, and proteostasis for conditions like cystic fibrosis and Gaucher disease.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Pharmacology
  • Drug Discovery

Background:

  • Protein misfolding is implicated in numerous severe diseases across various therapeutic areas.
  • Understanding the biological pathways of protein misfolding is crucial for developing effective treatments.
  • Small molecule therapeutics are gaining traction for targeting protein misfolding.

Purpose of the Study:

  • To survey current small molecules that modulate protein misfolding, stabilization, or proteostasis.
  • To discuss specific targets including CFTR and glucocerebrosidase.
  • To review approaches for modulating toxic oligomers, serum amyloid P (SAP), and HSF1 activators.

Main Methods:

  • Literature review of small molecules targeting protein misfolding.
  • Analysis of compounds affecting protein folding pathways.
  • Examination of therapeutic strategies for proteostasis modulation.

Main Results:

  • Identification of various small molecules with the potential to correct protein misfolding.
  • Discussion of therapeutic interventions for specific targets like CFTR and glucocerebrosidase.
  • Overview of strategies targeting toxic protein aggregates and enhancing cellular defense mechanisms.

Conclusions:

  • Small molecules represent a promising therapeutic avenue for protein misfolding diseases.
  • Targeting specific proteins and pathways offers potential for disease treatment.
  • Further research into small molecule modulators can advance proteostasis-based therapies.