A novel P159L mutation in the Parkin gene related to autosomal dominantly inherited late onset parkinsonism and protein aggregation

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
R Krüger ◽  
FP Marx ◽  
D Berg ◽  
C Holzmann ◽  
T Müller ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Late Onset ◽  
Parkin Gene

scholarly journals A quantitative model of human neurodegenerative diseases involving protein aggregation

2019 ◽  
Author(s):  
Kasper P. Kepp
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Late Onset ◽  
Cost Minimization ◽  
Quantitative Model ◽  
Cognitive Status ◽  
Cognitive Capability ◽  
Molecular Action ◽  
Direct Energy ◽  
Molecular Mode

AbstractHuman neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis involve protein aggregation and share many other similarities. It is widely assumed that the protein aggregates exhibit a specific molecular mode of toxic action. This paper presents a simple mathematical model arguing that clinical cognitive status relates to the energy available after subtracting cell maintenance due to general turnover of the misfolded proteins, rather than a specific toxic molecular action per se. Proteomic cost minimization can explain why highly expressed proteins changed less during evolution, leaving more energy for reproducing microorganisms on longer evolutionary timescales. In higher organisms, the excess energy instead defines cognitive capability, and the same equations remarkably apply. Proteomic cost minimization can explain why late-onset neurodegenerative diseases involve protein aggregation. The model rationalizes clinical ages of symptom onset for patients carrying pathogenic protein mutations: Unstable or aggregation-prone mutations confer a direct energy cost of turnover, but other risk modifiers also change the available cellular energy as ultimately defining clinical outcome. Proteomic cost minimization is consistent with current views on biomarker histories, explains conflicting data on overexpression models, and is supported by specific experiments showing that proteasome activity is required to confer toxicity to pathogenic mutants. The mechanism and model lend promise to a quantitative personalized medicine of neurodegenerative disease.

The parkin gene is not involved in late-onset Parkinson's disease

Neurology ◽  
2002 ◽  
Vol 58 (5) ◽  
pp. 835-835 ◽  
Author(s):  
M. Kann ◽  
K. Hedrich ◽  
P. Vieregge ◽  
H. Jacobs ◽  
B. Muller ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Onset ◽  
Parkin Gene

The parkin gene is not a major susceptibility locus for typical late-onset Parkinson's disease

2001 ◽  
Vol 22 (1) ◽  
pp. 73-74 ◽  
Author(s):  
R. L. Oliveri ◽  
M. Zappia ◽  
G. Annesi ◽  
F. Annesi ◽  
P. Spadafora ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Onset ◽  
Susceptibility Locus ◽  
Parkin Gene

Parkin gene variations in late-onset Parkinson's disease: comparison between Norwegian and German cohorts

2006 ◽  
Vol 113 (1) ◽  
pp. 9-13 ◽  
Author(s):  
A. M. Schlitter ◽  
M. Kurz ◽  
J. P. Larsen ◽  
D. Woitalla ◽  
T. Muller ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Onset ◽  
Parkin Gene

scholarly journals Methylene blue inhibits nucleation and elongation of SOD1 amyloid fibrils

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9719
Author(s):  
Greta Musteikyte ◽  
Mantas Ziaunys ◽  
Vytautas Smirnovas
Keyword(s):  
Methylene Blue ◽  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Amyloid Fibrils ◽  
Late Onset ◽  
Amyloid Aggregation ◽  
Amyloidogenic Proteins ◽  
Lateral Sclerosis

Protein aggregation into highly-structured amyloid fibrils is linked to several neurodegenerative diseases. Such fibril formation by superoxide dismutase I (SOD1) is considered to be related to amyotrophic lateral sclerosis, a late-onset and fatal disorder. Despite much effort and the discovery of numerous anti-amyloid compounds, no effective cure or treatment is currently available. Methylene blue (MB), a phenothiazine dye, has been shown to modulate the aggregation of multiple amyloidogenic proteins. In this work we show its ability to inhibit both the spontaneous amyloid aggregation of SOD1 as well as elongation of preformed fibrils.

scholarly journals Ageing and protein aggregation-mediated disorders: from invertebrates to mammals

2011 ◽  
Vol 366 (1561) ◽  
pp. 94-98 ◽  
Author(s):  
Andrew Dillin ◽  
Ehud Cohen
Keyword(s):  
Protein Aggregation ◽  
Mouse Models ◽  
Therapeutic Approach ◽  
Late Onset ◽  
Signalling Pathway ◽  
Toxic Protein ◽  
Novel Studies ◽  
The Past ◽  
Emergence Patterns ◽  
The Brain

Late onset is a common hallmark character of numerous disorders including human neurodegenerative maladies such as Huntington's, Parkinson's and Alzheimer's diseases. Why these diseases manifest in aged individuals and why distinct disorders share strikingly similar emergence patterns were until recently unsolved enigmas. During the past decade, invertebrate-based studies indicated that the insulin/IGF signalling pathway (IIS) mechanistically links neurodegenerative-associated toxic protein aggregation and ageing; yet, until recently it was unclear whether this link is conserved from invertebrates to mammals. Recent studies performed in Alzheimer's mouse models indicated that ageing alteration by IIS reduction slows the progression of Alzheimer's-like disease, protects the brain and mitigates the behavioural, pathological and biochemical impairments associated with the disease. Here, we review these novel studies and discuss the potential of ageing alteration as a therapeutic approach for the treatment of late onset neurodegeneration.

The parkin gene is not involved in late-onset Parkinson's disease

Neurology ◽  
2001 ◽  
Vol 57 (2) ◽  
pp. 359-362 ◽  
Author(s):  
R.L. Oliveri ◽  
M. Zappia ◽  
G. Annesi ◽  
D. Bosco ◽  
F. Annesi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Onset ◽  
Parkin Gene

Protein Aggregation and Pathogenesis of Huntingtons Disease: Mechanisms and Correlations

2000 ◽  
Vol 381 (9-10) ◽  
pp. 937-942 ◽  
Author(s):  
Erich E. Wanker
Keyword(s):  
Protein Aggregation ◽  
Disease Progression ◽  
Late Onset ◽  
Muscular Atrophy ◽  
Model Systems ◽  
Glutamine Repeat ◽  
Characteristic Features ◽  
Spinal Bulbar Muscular Atrophy

Abstract The formation of insoluble protein aggregates is a hallmark of Huntington's disease (HD) and related neurodegenerative disorders, such as dentatorubral pallidoluysian atrophy (DRPLA), spinal bulbar muscular atrophy (SBMA) and the spinocerebellar ataxia (SCA) type 1, 2, 3, 6 and 7. These disorders are caused by an expanded polyglutamine (polyQ) tract in otherwise unrelated proteins. They are characterized by late-onset, selective neuropathology, a pathogenic polyQ threshold and a relationship between polyQ length and disease progression. Thus, molecular models of HD and related glutamine-repeat disorders must account for these characteristic features. During the last three years, considerable effort has been invested in the development of in vitro and in vivo model systems to study the mechanisms of protein aggregation in glutamine-repeat disorders and its potential effects on disease progression and neurodegeneration. A selection of these studies is reviewed here. Furthermore, the correlation between aggregate formation and development of HD is discussed.

scholarly journals Cognitive alterations in juvenile Parkinson´s disease caused by the C212Y mutation in the Parkin gene.

2010 ◽  
Vol 3 (2) ◽  
pp. 55-62
Author(s):  
Sonia Moreno ◽  
Omar Buriticá ◽  
Alejandro Franco ◽  
Nicolás Pineda ◽  
William Arias ◽  
...  
Keyword(s):  
Late Onset ◽  
Phenotypic Expression ◽  
Neuropsychological Evaluation ◽  
Parkin Gene ◽  
Memory And Attention ◽  
Slowing Down ◽  
Functional Involvement ◽  
Slow Evolution ◽  
State Examination ◽  
Cognitive Alterations

In Antioquia, Colombia, four families have been reported with juvenile Parkinson´s disease and carrying the C212Y mutation in the Parkin gene. Many cognitive alterations associated with idiopathic, late-onset Parkinson´s disease have been described; however, little attention has been paid to the description of neuropsychological profiles in families carrying mutations in genes associated with juvenile Parkinson´s disease. For this study we selected a group of ten homozygous carriers of Parkin mutation C212Y with the clinical and a group of molecular diagnosis of Parkinson´s disease, and ten healthy relatives as controls. The neuropsychological evaluation revealed statistically significant differences between the two groups (p < 0.05) in Minimental State Examination and in tests evaluating working memory and attention in which prolonged execution times and marked slowing down of information processing were observed. We suggest that the observed alterations could be considered as neuropsychological features of patients with the C212Y mutation in the Parkin gene, the phenotypic expression of which seems to be associated in this population with slow evolution, mild cognitive impairment and functional involvement.

An Ultra-Structural Study of Human Melanoma in Vivo and Vitro

1976 ◽  
Vol 34 ◽  
pp. 258-259
Author(s):  
James R. Gaylor ◽  
Fredda Schafer ◽  
Robert E. Nordquist
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Apparatus ◽  
Protein Aggregation ◽  
Structural Study ◽  
Human Melanoma ◽  
Protein Matrix ◽  
Early Form ◽  
Endoplasmic Reticulum Protein ◽  
Mitochondrial Origin

Several theories on the origin of the melanosome exist. These include the Golgi origin theory, in which a tyrosinase-rich protein is "packaged" by the Golgi apparatus, thus forming the early form of the melanosome. A second theory postulates a mitochondrial origin of melanosomes. Its author contends that the melanosome is a modified mitochondria which acquires melanin during its development. A third theory states that a pre-melanosome is formed in the smooth or rough endoplasmic reticulum. Protein aggregation is suggested by one author as a possible source of the melanosome. This fourth theory postulates that the melanosome originates when the protein products of several genetic loci aggregate in the cytoplasm of the melanocyte. It is this protein matrix on which the melanin is deposited. It was with these theories in mind that this project was undertaken.

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