scholarly journals SOD1‐associated ALS: A promising system for elucidating the origin of protein‐misfolding disease

HFSP Journal ◽  
2008 ◽  
Vol 2 (6) ◽  
pp. 354-364 ◽  
Author(s):  
Anna Nordlund ◽  
Mikael Oliveberg
Keyword(s):  
Protein Misfolding ◽  
Misfolding Disease

scholarly journals Type 2 diabetes as a protein misfolding disease

2015 ◽  
Vol 21 (7) ◽  
pp. 439-449 ◽  
Author(s):  
Abhisek Mukherjee ◽  
Diego Morales-Scheihing ◽  
Peter C. Butler ◽  
Claudio Soto
Keyword(s):  
Type 2 Diabetes ◽  
Protein Misfolding ◽  
Misfolding Disease

Recent Studies on Design and Development of Drugs Against Alzheimer’s Disease (AD) Based on Inhibition of BACE-1 and Other AD-causative Agents

2020 ◽  
Vol 20 (13) ◽  
pp. 1195-1213 ◽  
Author(s):  
Satya P. Gupta ◽  
Vaishali M. Patil
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Protein Misfolding ◽  
Inhibition Mechanism ◽  
Design And Development ◽  
Causative Agents ◽  
Misfolding Disease ◽  
Structural Aspects

Background: Alzheimer’s disease (AD) is one of the neurodegenerative diseases and has been hypothesized to be a protein misfolding disease. In the generation of AD, β-secretase, γ-secretase, and tau protein play an important role. A literature search reflects ever increasing interest in the design and development of anti-AD drugs targeting β-secretase, γ-secretase, and tau protein. Objective: The objective is to explore the structural aspects and role of β-secretase, γ-secretase, and tau protein in AD and the efforts made to exploit them for the design of effective anti-AD drugs. Methods: The manuscript covers the recent studies on design and development of anti-AD drugs exploiting amyloid and cholinergic hypotheses. Results: Based on amyloid and cholinergic hypotheses, effective anti-AD drugs have been searched out in which non-peptidic BACE1 inhibitors have been most prominent. Conclusion: Further exploitation of the structural aspects and the inhibition mechanism for β-secretase, γ-secretase, and tau protein and the use of cholinergic hypothesis may lead still more potent anti-AD drugs.

Atherosclerosis: another protein misfolding disease?

2002 ◽  
Vol 8 (8) ◽  
pp. 370-374 ◽  
Author(s):  
Fulvio Ursini ◽  
Kelvin J.A Davies ◽  
Matilde Maiorino ◽  
Tiziana Parasassi ◽  
Alex Sevanian
Keyword(s):  
Protein Misfolding ◽  
Misfolding Disease

scholarly journals The Role of Activity in Synaptic Degeneration in a Protein Misfolding Disease, Prion Disease

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41182 ◽  
Author(s):  
Matteo Caleo ◽  
Laura Restani ◽  
Eleonora Vannini ◽  
Zuzana Siskova ◽  
Hussain Al-Malki ◽  
...  
Keyword(s):  
Prion Disease ◽  
Protein Misfolding ◽  
Synaptic Degeneration ◽  
Misfolding Disease

GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding, self-association and cellular degradation

2014 ◽  
Vol 382 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Maria Negahdar ◽  
Ingvild Aukrust ◽  
Janne Molnes ◽  
Marie H. Solheim ◽  
Bente B. Johansson ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Self Association ◽  
Misfolding Disease

scholarly journals Immunoglobulin light chain amyloid aggregation

2018 ◽  
Vol 54 (76) ◽  
pp. 10664-10674 ◽  
Author(s):  
Luis M. Blancas-Mejia ◽  
Pinaki Misra ◽  
Christopher J. Dick ◽  
Shawna A. Cooper ◽  
Keely R. Redhage ◽  
...  
Keyword(s):  
Light Chain ◽  
Protein Misfolding ◽  
Al Amyloidosis ◽  
Amyloid Aggregation ◽  
Immunoglobulin Light Chain ◽  
Misfolding Disease

Light chain (AL) amyloidosis is a devastating, complex, and incurable protein misfolding disease.

scholarly journals Role of domain interactions in the aggregation of full-length immunoglobulin light chains

2018 ◽  
Vol 116 (3) ◽  
pp. 854-863 ◽  
Author(s):  
Enrico Rennella ◽  
Gareth J. Morgan ◽  
Jeffery W. Kelly ◽  
Lewis E. Kay
Keyword(s):  
Protein Misfolding ◽  
Protective Role ◽  
Full Length ◽  
Free Energies ◽  
Patient Death ◽  
Domain Interactions ◽  
Amyloid Light Chain ◽  
The Stability ◽  
Misfolding Disease

Amyloid light-chain (LC) amyloidosis is a protein misfolding disease in which the aggregation of an overexpressed antibody LC from a clonal plasma cell leads to organ toxicity and patient death if left untreated. While the overall dimeric architecture of LC molecules is established, with each LC composed of variable (VL) and constant (CL) domains, the relative contributions of LC domain–domain interfaces and intrinsic domain stabilities to protection against LC aggregation are not well understood. To address these topics we have engineered a number of domain-destabilized LC mutants and used solution NMR spectroscopy to characterize their structural properties and intrinsic stabilities. Moreover, we used fluorescence spectroscopy to assay their aggregation propensities. Our results point to the importance of both dimerization strength and intrinsic monomer stability in stabilizing VL domains against aggregation. Notably, in all cases considered VL domains aggregate at least 10-fold faster than full-length LCs, establishing the important protective role of CL domains. A strong protective coupling is found between VL–VL and CL–CL dimer interfaces, with destabilization of one interface adversely affecting the stability of the other. Fibril formation is observed when either the VL or CL domain in the full-length protein is severely destabilized (i.e., where domain unfolding free energies are less than 2 kcal/mol). The important role of CL domains in preventing aggregation highlights the potential of the CL–CL interface as a target for the development of drugs to stabilize the dimeric LC structure and hence prevent LC amyloidosis.

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