scholarly journals α-Synuclein Strains: Does Amyloid Conformation Explain the Heterogeneity of Synucleinopathies?

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 931
Author(s):  
Simon Oliver Hoppe ◽  
Gamze Uzunoğlu ◽  
Carmen Nussbaum-Krammer
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Sequence ◽  
Heterogeneous Group ◽  
Prion Strain ◽  
Amyloid Deposits ◽  
Growing Body ◽  
Single Protein ◽  
Causative Agents ◽  
Amyloid Structures

Synucleinopathies are a heterogeneous group of neurodegenerative diseases with amyloid deposits that contain the α-synuclein (SNCA/α-Syn) protein as a common hallmark. It is astonishing that aggregates of a single protein are able to give rise to a whole range of different disease manifestations. The prion strain hypothesis offers a possible explanation for this conundrum. According to this hypothesis, a single protein sequence is able to misfold into distinct amyloid structures that can cause different pathologies. In fact, a growing body of evidence suggests that conformationally distinct α-Syn assemblies might be the causative agents behind different synucleinopathies. In this review, we provide an overview of research on the strain hypothesis as it applies to synucleinopathies and discuss the potential implications for diagnostic and therapeutic purposes.

scholarly journals Remodeling Alzheimer-amyloidosis models by seeding

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Brittany S. Ulm ◽  
David R. Borchelt ◽  
Brenda D. Moore
Keyword(s):  
Amyloid Precursor Protein ◽  
Neurodegenerative Diseases ◽  
Amyloid Beta ◽  
Precursor Protein ◽  
Time Interval ◽  
Murine Models ◽  
Brain Pathology ◽  
Amyloid Deposits ◽  
Transgenic Murine Models ◽  
Mutant Genes

AbstractAlzheimer’s disease (AD) is among the most prevalent neurodegenerative diseases, with brain pathology defined by extracellular amyloid beta deposits and intracellular tau aggregates. To aid in research efforts to improve understanding of this disease, transgenic murine models have been developed that replicate aspects of AD pathology. Familial AD is associated with mutations in the amyloid precursor protein and in the presenilins (associated with amyloidosis); transgenic amyloid models feature one or more of these mutant genes. Recent advances in seeding methods provide a means to alter the morphology of resultant amyloid deposits and the age that pathology develops. In this review, we discuss the variety of factors that influence the seeding of amyloid beta pathology, including the source of seed, the time interval after seeding, the nature of the transgenic host, and the preparation of the seeding inoculum.

Mechanistic roles for altered O-GlcNAcylation in neurodegenerative disorders

2021 ◽  
Vol 478 (14) ◽  
pp. 2733-2758
Author(s):  
Aaron T. Balana ◽  
Matthew R. Pratt
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Posttranslational Modification ◽  
Protein Quality ◽  
Neuronal Dysfunction ◽  
Neuronal Communication ◽  
Programmed Death ◽  
Growing Body ◽  
Potential Strategy ◽  
Therapeutic Avenue

Neurodegenerative diseases such as Alzheimer's and Parkinson's remain highly prevalent and incurable disorders. A major challenge in fully understanding and combating the progression of these diseases is the complexity of the network of processes that lead to progressive neuronal dysfunction and death. An ideal therapeutic avenue is conceivably one that could address many if not all of these multiple misregulated mechanisms. Over the years, chemical intervention for the up-regulation of the endogenous posttranslational modification (PTM) O-GlcNAc has been proposed as a potential strategy to slow down the progression of neurodegeneration. Through the development and application of tools that allow dissection of the mechanistic roles of this PTM, there is now a growing body of evidence that O-GlcNAc influences a variety of important neurodegeneration-pertinent mechanisms, with an overall protective effect. As a PTM that is appended onto numerous proteins that participate in protein quality control and homeostasis, metabolism, bioenergetics, neuronal communication, inflammation, and programmed death, O-GlcNAc has demonstrated beneficence in animal models of neurodegenerative diseases, and its up-regulation is now being pursued in multiple clinical studies.

Interaction of monomeric and self-assembled aromatic amino acids with model membranes: self-reproduction phenomena

2019 ◽  
Vol 55 (100) ◽  
pp. 15109-15112 ◽  
Author(s):  
Soumya Kanti De ◽  
Anjan Chakraborty
Keyword(s):  
Amino Acids ◽  
Neurodegenerative Diseases ◽  
Aromatic Amino Acids ◽  
Model Membranes ◽  
Spontaneous Formation ◽  
Self Assembled ◽  
Amyloid Structures

The spontaneous formation of amyloid structures of proteins is responsible for several major human neurodegenerative diseases.

scholarly journals Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Martin Nors Pedersen ◽  
Vito Foderà ◽  
Istvan Horvath ◽  
Andreas van Maarschalkerweerd ◽  
Katrine Nørgaard Toft ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Small Angle ◽  
Alpha Synuclein ◽  
X Ray ◽  
Transient Nature ◽  
X Ray Scattering ◽  
Amyloid Deposits ◽  
Potential Link ◽  
Presence And Absence

Abstract Aggregation of proteins into amyloid deposits is the hallmark of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The suggestion that intermediate oligomeric species may be cytotoxic has led to intensified investigations of pre-fibrillar oligomers, which are complicated by their transient nature and low population. Here we investigate alpha-synuclein oligomers, enriched by a 2-pyridone molecule (FN075) and the conversion of oligomers into fibrils. As probed by leakage assays, the FN075 induced oligomers potently disrupt vesicles in vitro, suggesting a potential link to disease related degenerative activity. Fibrils formed in the presence and absence of FN075 are indistinguishable on microscopic and macroscopic levels. Using small angle X-ray scattering, we reveal that FN075 induced oligomers are similar, but not identical, to oligomers previously observed during alpha-synuclein fibrillation. Since the levels of FN075 induced oligomers correlate with the amounts of fibrils among different FN075:protein ratios, the oligomers appear to be on-pathway and modeling supports an ‘oligomer stacking model’ for alpha-synuclein fibril elongation.

scholarly journals Pick’s disease and subdural haematoma: A diagnostic red herring

2019 ◽  
Vol 5 (1) ◽  
pp. 141-145
Author(s):  
Philip Adebayo ◽  
Funmilola Taiwo ◽  
Fatma Bakshi ◽  
Sunham Nur
Keyword(s):  
Neurodegenerative Diseases ◽  
Cognitive Decline ◽  
Frontotemporal Dementia ◽  
Subdural Haematoma ◽  
Chronic Subdural Haematoma ◽  
Heterogeneous Group ◽  
Pick's Disease ◽  
Pick’S Disease ◽  
Temporal Lobes ◽  
Executive Skills

Frontotemporal dementia (FTD), otherwise known as Pick’s disease, is a clinically heterogeneous group of sporadic and familial neurodegenerative diseases. These conditions are characterized by dementia, behavioural and language dysfunction and loss of executive skills resulting from the degeneration of the frontal and temporal lobes. Although reversible causes of dementia are always sought during the evaluation of patients with progressive cognitive decline, the occurrence of a reversible aetiology may distract from evaluating for neurodegenerative causes of dementia. This report is about a 66-year old man with features of FTD and superimposed chronic subdural haematoma.

scholarly journals Algorithm to find distant repeats in a single protein sequence

2008 ◽  
Vol 3 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Nirjhar Banerjee ◽  
Rangarajan Sarani ◽  
Chellamuthu Vasuki Ranjani ◽  
Govindaraj Sowmiya ◽  
Daliah Michael ◽  
...  
Keyword(s):  
Protein Sequence ◽  
Single Protein

Genetic and antigenic diversity ofTheileria parvain cattle in Eastern and Southern zones of Tanzania. A study to support control of East Coast fever

Parasitology ◽  
2014 ◽  
Vol 142 (5) ◽  
pp. 698-705 ◽  
Author(s):  
MWEGA ELISA ◽  
SALIH DIA HASAN ◽  
NJAHIRA MOSES ◽  
RUKAMBILE ELPIDIUS ◽  
ROBERT SKILTON ◽  
...  
Keyword(s):  
Protein Sequence ◽  
East Coast ◽  
Geographical Origin ◽  
East Coast Fever ◽  
Control Measures ◽  
Target Antigen ◽  
Antigenic Diversity ◽  
Cell Target ◽  
Single Protein ◽  
High Level

SUMMARYThis study investigated the genetic and antigenic diversity ofTheileria parvain cattle from the Eastern and Southern zones of Tanzania. Thirty-nine (62%) positive samples were genotyped using 14 mini- and microsatellite markers with coverage of all fourT. parvachromosomes. Wright'sFindex (FST = 0 × 094) indicated a high level of panmixis. Linkage equilibrium was observed in the two zones studied, suggesting existence of a panmyctic population. In addition, sequence analysis of CD8+T-cell target antigen genes Tp1 revealed a single protein sequence in all samples analysed, which is also present in theT. parvaMuguga strain, which is a component of the FAO1 vaccine. All Tp2 epitope sequences were identical to those in theT. parvaMuguga strain, except for one variant of a Tp2 epitope, which is found inT.parva Kiambu 5 strain, also a component the FAO1 vaccine. Neighbour joining tree of the nucleotide sequences of Tp2 showed clustering according to geographical origin. Our results show low genetic and antigenic diversity ofT. parvawithin the populations analysed. This has very important implications for the development of sustainable control measures forT. parvain Eastern and Southern zones of Tanzania, where East Coast fever is endemic.

scholarly journals Biochemical Biomarkers and Neurodegenerative Diseases

2021 ◽  
Vol 11 (7) ◽  
pp. 940
Author(s):  
Marcello Ciaccio
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Peripheral Nervous System ◽  
Heterogeneous Group ◽  
Biochemical Biomarkers ◽  
The Central Nervous System

Neurodegenerative diseases (ND) are a heterogeneous group of disorders characterized by progressive dysfunction and loss of neurons in different areas of the central nervous system or peripheral nervous system [...]

scholarly journals Prion-like spread of protein aggregates in neurodegeneration

2012 ◽  
Vol 209 (5) ◽  
pp. 889-893 ◽  
Author(s):  
Magdalini Polymenidou ◽  
Don W. Cleveland
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Recent Work ◽  
Protein Misfolding ◽  
Protein Aggregates ◽  
Misfolded Protein ◽  
Cell Aggregate ◽  
Protein Assemblies ◽  
Parkinson’S Diseases ◽  
Growing Body

Protein misfolding is common to most neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. Recent work using animal models with intracellular α-synuclein and tau inclusions adds decisively to a growing body of evidence that misfolded protein aggregates can induce a self-perpetuating process that leads to amplification and spreading of pathological protein assemblies. When coupled with the progressive nature of neurodegeneration, recognition of such cell-to-cell aggregate spread suggests a unifying mechanism underlying the pathogenesis of these disorders.

scholarly journals Apolipoprotein E Genotypes in Mexican Patients with Parkinson's Disease

2009 ◽  
Vol 27 (5) ◽  
pp. 225-230 ◽  
Author(s):  
M.P. Gallegos-Arreola ◽  
L.E. Figuera ◽  
G.G. Ortiz ◽  
F.J. Jiménez-Gil ◽  
J. Ramírez-Vega ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Odds Ratio ◽  
Age Group ◽  
Amyloid Deposits ◽  
Increased Risk ◽  
Apo E ◽  
Apolipoprotein E Genotypes ◽  
Risk Effect

Background: The association of the apolipoprotein (Apo E) -epsilon4 allele to neurodegenerative diseases such as Parkinson’s disease (PD) has been analyzed in several studies. This association has been identified by amyloid deposits and neurofibrillary tangles in the brains of patients with neurodegenerative diseases.Method: In this study the possible relationship betweenApo Ealleles and PD patients was analyzed in 105 patients with PD and 107 healthy controls from a Mexican population.Results: Allele analysis in PD vs. controls was: ε2in 6% and 2.3%, respectively; ε3in 73% and 88.3%; and ε4in 21% and 9.4%. The ε3allele showed a protective risk effect with an Odds ratio (OR) of 0.36 (95%CI 0.20-0.61) and p < 0.05; contrary results were observed for the ε4allele, which showed an increased risk for PD, with an OR of 2.57(95% CI 1.42-4.79) andp< 0.05. Upon multivariate analysis showed PD risk was evident in patients who were carriers of the genotype ε3/ε4; age group (fifty or more years) and had exposure to pesticides and solvents (p< 0.05).Conclusions: The ε3/ε3; ε3/ε4genotypes of the Apo E, were positively associated with sporadic PD.

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