Article
Biochemistry & Molecular Biology
Jaime Santos, Irantzu Pallares, Valentin Iglesias, Salvador Ventura
Summary: The prevalence of cryptic amyloidogenic regions (CARs) of polar nature in intrinsically disordered regions (IDRs) has been explored. CARs are associated with protein function and interactions, but also carry a risk of malfunction. The existence of ancestral CARs may have evolved into functional interacting regions, playing a significant role in protein evolution at the origins of life.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Physical
Souvik Dey, Matthew MacAinsh, Huan-Xiang Zhou
Summary: For intrinsically disordered proteins (IDPs), the dynamics of the backbone play a key role in encoding their function. The dynamics are regulated by local interactions, secondary structures, and glycines. These sequence-dependent changes in backbone dynamics allow IDPs to respond to binding partners in a versatile manner.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Medicinal
Souvik Mondal, Krishna Prasad Ghanta, Sanjoy Bandyopadhyay
Summary: This study investigates the dynamic properties of water near the α-synuclein protein associated with Parkinson's disease. The results show that the translational and rotational mobility of water molecules near the peptide segments are significantly restricted, with water near the hydrophobic segment exhibiting more restricted diffusivity. The time scales of peptide-water and water-water hydrogen bond relaxations correlate with the diffusion of interfacial water molecules. The hindered dynamic environment near a specific segment can enhance early stages of peptide aggregation.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Review
Pharmacology & Pharmacy
Samuel Pena-Diaz, Javier Garcia-Pardo, Salvador Ventura
Summary: Parkinson's disease is the second most common neurodegenerative disorder worldwide, characterized by protein deposits in dopaminergic neurons. Recent research has identified compounds primarily of an aromatic nature that target a-Syn aggregation. This study provides a historical overview of Parkinson's disease, its molecular aspects, and current trends in small compound development to address a-Syn aggregation. These compounds are promising for the development of effective therapies for Parkinson's disease.
Article
Chemistry, Multidisciplinary
Souvik Mondal, Sandip Mondal, Sanjoy Bandyopadhyay
Summary: The study found that the R6 unit of the peptide is relatively rigid and has weak interactions with water molecules, potentially serving as a nucleation site for the aggregation process. Additionally, there are highly ordered and relatively disordered water molecules at the interface, where the ordered ones facilitate water-mediated interactions between peptide monomers while the disordered ones may be easily expelled, promoting direct peptide-peptide interactions during the aggregation process.
Article
Chemistry, Multidisciplinary
Xidong Li, Qiushi Li, Yanhui Zhang, Yang Bai, Yue Cao, Yang Yang, Lie Zang, Meiyi Huang, Rubo Sui
Summary: This study investigated the effects of NiO NPs on protein aggregation and found that NiO NPs accelerated the formation of α-synuclein amyloids and enhanced their cytotoxicity. Through a series of analyses, the results showed that the interaction between NiO NPs and α-synuclein exacerbated the development of neuroadaptive diseases.
ARABIAN JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Julien Mignon, Denis Mottet, Tanguy Leyder, Vladimir N. Uversky, Eric A. Perpete, Catherine Michaux
Summary: This study thoroughly characterized the structural properties and aggregation behavior of DPF3a and DPF3b isoforms. It was found that DPF3a is more disordered and exhibits more expanded conformations compared to DPF3b. Both isoforms can aggregate into amyloid fibrils, but DPF3a fibrillates at a faster rate.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Biochemistry & Molecular Biology
Rakesh Trivedi, Hampapathalu Adimurthy Nagarajaram
Summary: This review discusses different aspects of disordered proteins and protein regions, as well as the experimental and computational methods used to characterize them. Additionally, the role of disordered proteins in diseases and their potential as drug targets are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Carlos Pintado-Grima, Oriol Barcenas, Zoe Manglano-Artunedo, Rita Vilaca, Sandra Macedo-Ribeiro, Irantzu Pallares, Jaime Santos, Salvador Ventura
Summary: Proteome-wide analyses have revealed that amyloidogenic regions are present in most globular proteins, while being underrepresented in intrinsically disordered proteins (IDPs). However, recent research has shown that intrinsically disordered regions (IDRs) do contain significant amyloid load in the form of cryptic amyloidogenic regions (CARs), which are exposed to solvent and are more polar than conventional amyloid regions. CARs are associated with both IDPs function and malfunction, and their presence is linked to pathologies such as cancer and Alzheimer's disease. To explore these previously unnoticed amyloidogenic regions, CARs-DB, a database containing precomputed predictions for all CARs in the IDPs deposited in the DisProt database, was developed. CARs-DB allows for easy access to a large number of unique CARs and has been validated by demonstrating the amyloidogenic potential of selected CARs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Medicine, General & Internal
E. Srinivasan, G. Chandrasekhar, P. Chandrasekar, K. Anbarasu, A. S. Vickram, Rohini Karunakaran, R. Rajasekaran, P. S. Srikumar
Summary: Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons, with pathogenesis linked to the misfolding and mutations of alpha-synuclein protein. Genetic and other factors lead to the formation of amyloid structures from alpha-synuclein, causing PD.
FRONTIERS IN MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
H. Jane Dyson
Summary: Viruses infect all kingdoms of life and employ disordered proteins to accomplish various functions. Disordered proteins have been discovered in almost all viruses studied, regardless of the viral genome composition or the viral capsid configuration. This review presents a collection of stories illustrating the diverse functions of disordered proteins in viruses, providing a survey of the field's expansion.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Samuel Naudi-Fabra, Maud Tengo, Malene Ringkjobing Jensen, Martin Blackledge, Sigrid Milles
Summary: Studying the conformational landscape of intrinsically disordered and partially folded proteins is challenging and requires an integrated approach using multiple techniques to accurately describe the conformational ensembles of these proteins. This integrated approach has been successfully tested and validated, providing new insights into the conformational landscape of viral proteins and demonstrating its potential for integrative dynamic structural biology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Biochemistry & Molecular Biology
Abbie T. Rodger, Maryam A. L. Nasser, Wayne G. Carter
Summary: Currently, there are no pharmacological treatments that can completely stop or reverse the progression of Parkinson's Disease (PD). Therefore, there is a need for neuroprotective therapies. This systematic review examines the effectiveness of anti-a-synuclein (a-syn) therapies in preventing PD progression in preclinical models and human clinical trials. The review found that novel preclinical anti-a-syn therapeutics reduced a-syn aggregations and protected against dopaminergic neuronal loss. Completed clinical trials showed significant tolerability and efficacy in reducing a-syn and minimal adverse effects. Overall, this review highlights the potential of anti-a-syn therapies in both preclinical and clinical settings to reduce a-syn accumulation and potentially slow down PD progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Edward Chau, Jin Ryoun Kim
Summary: This study investigated the interactions between Aβ42 and αS in different conformations. It was found that αS monomers and oligomers promoted the oligomerization and stabilization of soluble Aβ42, while αS fibrils hindered the aggregation of Aβ42. These interactions may be achieved through direct binding or co-assembly, and different parts of Aβ42 mediated the interactions with αS.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Erwan Bezard
Summary: This opinion paper addresses the issue of conceptual sloppiness and poor methodological characterization in Parkinson's disease research, emphasizing its negative impact on progress and proposing a remedy.