Pathological Protein Aggregation

A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION; POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.

Also Known As:

Networked: 34 relevant articles (2 outcomes, 2 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Alzheimer Disease (Alzheimer's Disease)
2.	Neurodegenerative Diseases (Neurodegenerative Disease)
3.	Amyloidosis
4.	Parkinson Disease (Parkinson's Disease)
5.	Neuroinflammatory Diseases

Experts

1.	Fürst, Dieter O: 3 articles (03/2013 - 06/2006)
2.	van der Ven, Peter F M: 3 articles (03/2013 - 06/2006)
3.	Bachurin, S O: 2 articles (01/2016 - 05/2014)
4.	Schröder, Rolf: 2 articles (03/2014 - 06/2006)
5.	Goldfarb, Lev G: 2 articles (03/2013 - 06/2006)
6.	Olivé, Montse: 2 articles (03/2013 - 06/2006)
7.	Loh, Doris: 1 article (09/2021)
8.	Reiter, Russel J: 1 article (09/2021)
9.	Beekes, Michael: 1 article (01/2021)
10.	Creamer, Daniel: 1 article (01/2021)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Pathological Protein Aggregation:

1.	Proteins (Proteins, Gene)FDA Link 10/13/2023 - "p62 has been suggested to sequester proteins through formation of liquid-like biomolecular condensates, but the physical mechanisms by which p62 condensates may regulate pathological protein aggregation remain unclear. " 09/05/2017 - "Studying liquid-liquid phase separation (LLPS) of proteins provides key insights into the biogenesis of membraneless organelles and pathological protein aggregation in disease. " 03/01/2013 - "Our analyses revealed altered expression of chaperone proteins and components of proteasomal and autophagic degradation pathways in abnormal muscle fibers that harbor protein deposits but not in neighboring muscle fibers without pathological protein aggregation. " 04/01/2006 - "The constitutive (HSP73) and (heat)-inducible (HSP72) proteins of the heat shock 70 family form a major defence system against pathological protein aggregation. " 05/01/2020 - "While studies on pathological protein aggregation are largely limited to neurodegenerative disease, emerging evidence suggests that other diseases are also associated with pathogenic protein aggregation. "
2.	PlectinIBA 03/01/2014 - "Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle."
3.	Peptides (Polypeptides)IBA 01/01/2019 - "We test the efficacy of our approach on experimental data for the aggregation of the amyloid-β(1-42) peptide of Alzheimer's disease in the model organism Caenorhabditis elegans Our results pose and answer the question of the link between the molecular basis of protein aggregation and optimal strategies for inhibiting it, opening up avenues for the design of rational therapies to control pathological protein aggregation."
4.	SynucleinsIBA 01/01/2020 - "Our data indicates the close association between IAPP and α-synuclein and the potential link between T2DM and PD, which implies that T2DM may facilitate PD disease onset and progress by interfering with the pathological protein aggregation both in the pancreatic islets and the brain." 01/01/2018 - "General significance These results, in addition to our previous studies on α-synuclein and GFAP, confirm the property of ceftriaxone to inhibit the pathological protein aggregation of lysozyme also by a chaperone-like mechanism, extending the potential therapeutic application of this molecule to some forms of human hereditary systemic amyloidosis." 10/01/2023 - "Here we discuss the role of phase separation of the neuronal proteins tau, α-synuclein, fused in sarcoma (FUS), and the transactive response DNA-binding protein of 43 kDa (TDP-43) that are associated with neurodegeneration in the context of pathological protein aggregation."
5.	Muramidase (Lysozyme)IBA 01/01/2018 - "General significance These results, in addition to our previous studies on α-synuclein and GFAP, confirm the property of ceftriaxone to inhibit the pathological protein aggregation of lysozyme also by a chaperone-like mechanism, extending the potential therapeutic application of this molecule to some forms of human hereditary systemic amyloidosis."
6.	Ceftriaxone (Ceftriaxon)FDA LinkGeneric 01/01/2018 - "General significance These results, in addition to our previous studies on α-synuclein and GFAP, confirm the property of ceftriaxone to inhibit the pathological protein aggregation of lysozyme also by a chaperone-like mechanism, extending the potential therapeutic application of this molecule to some forms of human hereditary systemic amyloidosis."
7.	alpha-SynucleinIBA 08/01/2007 - "The finding of statistically lower ubiquitination of the mutant alpha-synuclein forms supports a role for this modification in the mechanism of pathological protein aggregation." 01/01/2021 - "Research has implicated alpha-synuclein (aSyn) in pathological protein aggregation observed in almost all patients with Parkinson's disease and more than 50% of patients with Alzheimer's disease. "
8.	tau Proteins (tau Protein)IBA 10/01/2023 - "Here we discuss the role of phase separation of the neuronal proteins tau, α-synuclein, fused in sarcoma (FUS), and the transactive response DNA-binding protein of 43 kDa (TDP-43) that are associated with neurodegeneration in the context of pathological protein aggregation." 01/01/2016 - "According to current concepts, AD is proteinopathy due to impairments in the metabolism of amyloid precursor protein and tau-protein that results in the pathological protein aggregation in the brain. "
9.	RNA-Binding Proteins (RNA-Binding Protein)IBA 10/10/2014 - "This discovery suggests that the regulated cellular pathway, which utilizes assembly of RNA binding proteins to package and silence mRNAs during stress, may be integral in the aberrant pathological protein aggregation that occurs in numerous neurodegenerative conditions." 01/01/2023 - "Many RNA-binding proteins (RBPs), particularly those associated with RNA granules, promote pathological protein aggregation in neurodegenerative diseases. "
10.	RNA (Ribonucleic Acid)IBA 01/01/2023 - "We present evidence for the following eight hallmarks of NDD: pathological protein aggregation, synaptic and neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. " 09/17/2021 - "Aberrant phase separation due to dysregulated membrane lipid rafts and/or PTMs, as well as the absence of adequate hydrotropic small molecules such as ATP, or the presence of specific RNA proteins can cause pathological protein aggregation in neurodegenerative disorders. "

Therapies and Procedures

1.

Therapeutics 01/01/2019 - "We test the efficacy of our approach on experimental data for the aggregation of the amyloid-β(1-42) peptide of Alzheimer's disease in the model organism Caenorhabditis elegans Our results pose and answer the question of the link between the molecular basis of protein aggregation and optimal strategies for inhibiting it, opening up avenues for the design of rational therapies to control pathological protein aggregation."