ReviewInternational journal of molecular sciences2018
Insights into the Molecular Mechanisms of Alzheimer's and Parkinson's Diseases with Molecular Simulations: Understanding the Roles of Artificial and Pathological Missense Mutations in Intrinsically Disordered Proteins Related to Pathology.
Review in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Neuroinflammation in Parkinson's Disease: From Gene to Clinic: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Differential proteostasis imbalance and the molecular basis of distinct synucleinopathies and tauopathies.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Current perspectives in drug targeting intrinsically disordered proteins and biomolecular condensates.BMC biology · 2025Review
- Liquid-Liquid Phase Separation Associated with Intrinsically Disordered Proteins: Experimental and Computational Tools.Current protein & peptide science · 2025Review
- Molecular Insights into Cu/Zn Metal Response to the Amyloid β-Peptide (1-42).ACS physical chemistry Au · 2024Article
- Review
- Review
- Review
- Editorial: From the hydrophobic core to the globular-disorder interface: New challenges and insights into protein design.Frontiers in molecular biosciences · 2023Article
- Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer's Disease from Other Neurological Disorders.International journal of molecular sciences · 2022Article
- Mutation-Specific Differences in Kv7.1 (International journal of molecular sciences · 2022Review
- Intrinsically disordered proteins and proteins with intrinsically disordered regions in neurodegenerative diseases.Biophysical reviews · 2022Review
- Current understandings and perspectives of petroleum hydrocarbons in Alzheimer's disease and Parkinson's disease: a global concern.Environmental science and pollution research international · 2022Review
- On the Dependence of Prion and Amyloid Structure on the Folding Environment.International journal of molecular sciences · 2021Article
- Protein folding, misfolding, and un/non-folding: overview of the SP16 Session at the 20Biophysical reviews · 2021Article
- Conformational distortion in a fibril-forming oligomer arrests alpha-Synuclein fibrillation and minimizes its toxic effects.Communications biology · 2021Article
- Impact of Mutations on the Conformational Transition from α-Helix to β-Sheet Structures in Arctic-Type AβACS omega · 2020Article
- The English (H6R) Mutation of the Alzheimer's Disease Amyloid-β Peptide Modulates Its Zinc-Induced Aggregation.Biomolecules · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid-β and α-synuclein are intrinsically disordered proteins (IDPs), which are at the center of Alzheimer's and Parkinson's disease pathologies, respectively. These IDPs are extremely flexible and do not adopt stable structures. Furthermore, both amyloid-β and α-synuclein can form toxic oligomers, amyloid fibrils and other type of aggregates in Alzheimer's and Parkinson's diseases. Experimentalists face challenges in investigating the structures and thermodynamic properties of these IDPs in their monomeric and oligomeric forms due to the rapid conformational changes, fast aggregation processes and strong solvent effects. Classical molecular dynamics simulations complement experiments and provide structural information at the atomic level with dynamics without facing the same experimental limitations. Artificial missense mutations are employed experimentally and computationally for providing insights into the structure-function relationships of amyloid-β and α-synuclein in relation to the pathologies of Alzheimer's and Parkinson's diseases. Furthermore, there are several natural genetic variations that play a role in the pathogenesis of familial cases of Alzheimer's and Parkinson's diseases, which are related to specific genetic defects inherited in dominant or recessive patterns. The present review summarizes the current understanding of monomeric and oligomeric forms of amyloid-β and α-synuclein, as well as the impacts of artificial and pathological missense mutations on the structural ensembles of these IDPs using molecular dynamics simulations. We also emphasize the recent investigations on residual secondary structure formation in dynamic conformational ensembles of amyloid-β and α-synuclein, such as β-structure linked to the oligomerization and fibrillation mechanisms related to the pathologies of Alzheimer's and Parkinson's diseases. This information represents an important foundation for the successful and efficient drug design studies.
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Registered trials
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