Neurodegenerative Diseases Journal Impact Factor & Information

Publisher: Karger

Journal description

Neurodegenerative Diseases is a bimonthly, multidisciplinary journal for the publication of advances in the understanding of neurodegenerative diseases, including Alzheimer disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington disease and related neurological and psychiatric disorders. Neurodegenerative Diseases publishes results from basic and clinical scientific research programs designed to better understand the normal functions of genes and proteins involved in neurodegenerative diseases, to characterize their role in pathogenic disease mechanisms, to model their functions in animals and to explore their roles in the diagnosis, treatment and prevention of neurodegenerative diseases. It is our firm belief that successful strategies for novel treatments of neurodegenerative diseases will emerge from the intelligent integration of basic neurobiology with clinical sciences. Therefore, Neurodegenerative Diseases will accept high-quality papers from a broad spectrum of scientific research areas ranging from molecular and cell biology to neuroscience, pharmacology, genetics and the clinical sciences.

Current impact factor: 3.51

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.511
2013 Impact Factor 3.454
2012 Impact Factor 3.41
2011 Impact Factor 3.056
2010 Impact Factor 3.791
2009 Impact Factor 3.496
2008 Impact Factor 2.989

Impact factor over time

Impact factor

Additional details

5-year impact 3.12
Cited half-life 4.00
Immediacy index 0.80
Eigenfactor 0.00
Article influence 0.92
Website Neurodegenerative Diseases website
Other titles Neuro-degenerative diseases
ISSN 1660-2862
OCLC 260107464
Material type Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • On author's server or institutional server
    • Server must be non-commercial
    • Publisher's version/PDF cannot be used
    • Publisher copyright and source must be acknowledged
    • Must link to publisher version
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Recent studies have demonstrated that arterial spin labeling magnetic resonance imaging (ASL-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) identify similar regional abnormalities and have comparable diagnostic accuracy in Alzheimer's disease (AD). The agreement between these modalities in the AD continuum, which is an important concept for early detection and disease monitoring, is yet unclear. Objective: We aimed to assess the ability of the cerebral blood flow (CBF) measures from ASL-MRI and cerebral metabolic rate for glucose (CMRgl) measures from FDG-PET to distinguish amyloid-β-positive (Aβ+) subjects in the AD continuum from healthy controls. Methods: The study included asymptomatic, cognitively normal (CN) controls and patients with early mild cognitive impairment (MCI), late MCI, and AD, all with significant levels of cortical Aβ based on their florbetapir PET scans to restrict the study to patients truly in the AD continuum. The discrimination power of each modality was based on the whole-brain patterns of CBF and CMRgl changes identified by partial least squares logistic regression, a multivariate analysis technique. Results: While CBF changes in the posterior inferior aspects of the brain and a pattern of CMRgl changes in the superior aspects of the brain including frontal and parietal regions best discriminated the Aβ+ subjects in the early disease stages from the Aβ- CN subjects, there was a greater agreement in the whole-brain patterns of CBF and CMRgl changes that best discriminated the Aβ+ subjects from the Aβ- CN subjects in the later disease stages. Despite the differences in the whole-brain patterns of CBF and CMRgl changes, the discriminative powers of both modalities were similar with statistically nonsignificant performance differences in sensitivity and specificity. Conclusion: The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Aβ+ subjects across the AD continuum compared with Aβ- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum.
    Neurodegenerative Diseases 11/2015; DOI:10.1159/000439257
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    ABSTRACT: Background: Determination of Alzheimer's disease (AD) by cerebrospinal fluid (CSF) biomarkers - 42-amino-acid amyloid-β (Aβ42), total tau and phosphorylated tau (p-tau) - has demonstrated high validity for detecting AD neuropathological changes. However, their prognostic utility to predict the onset of dementia in predementia subjects is still questioned. We aimed to study the prospective clinical evolution of a group of subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) and to determine the prognostic capacity of AD CSF biomarkers. Methods: 149 subjects with MCI or SCD, not meeting dementia criteria, underwent a prospective clinical, neuropsychological and CSF biomarker study. Patients were initially classified as SCD or MCI following internationally accepted criteria. CSF sampling was obtained and analysed following consensus protocols. Neuropsychological and clinical evaluations were conducted at the follow-up. Statistical analysis considering the final clinical diagnosis, regression analysis to define risk factors and survival curves for progression were made. Results: 72.4% of subjects (83% MCI and 27% SCD) with a pathological CSF ratio (Aβ42/p-tau) met criteria for dementia during the 5-year follow-up versus 18.7% of subjects from the group with a normal ratio. The pathological CSF ratio was a powerful marker of risk for AD dementia (OR 27.1; 95% CI 10.3-71.2). Kaplan-Meier survival curves showed that only 15% of subjects with a pathological CSF ratio remained free of AD dementia at 5 years of follow-up. All subjects who reverted to normal cognition presented a normal CSF profile at baseline. Conclusion: An abnormal AD CSF biomarker profile in predementia subjects is a powerful predictor of cognitive and/or functional decline in the medium term.
    Neurodegenerative Diseases 11/2015; DOI:10.1159/000439258
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    ABSTRACT: Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex physiopathology and still undefined initiators. Several risk factors have been suggested for AD with recent evidence supporting an etiopathogenic role of chronic environmental stress and glucocorticoids (GCs, stress hormones) in the development of the disease. Indeed, both AD and chronic stress are associated with neuronal atrophy, synaptic loss and cognitive impairment. Our previous studies have demonstrated the aggravating role of stress and GCs on AD pathology, including Tau hyperphosphorylation and aggregation and cognitive deficits in various AD models. In light of the suggested involvement of Tau missorting in AD synaptotoxity and the dual cytoplasmic and synaptic role of Tau, our recent studies focused on the possible role of Tau in the underlying cascades of stress/GC neuronal malfunction/atrophy in wild-type animals by monitoring the intracellular localization of Tau and its phosphorylation status in different cellular compartments. Summary: Biochemical, ultrastructural, behavioral and neurostructural analysis have helped demonstrate that prolonged GC administration leads to dendritic remodeling and spine atrophy and loss in the rat hippocampus triggering Tau missorting at hippocampal synapses with the participation of specific phosphorylated Tau isoforms in this synaptic accumulation. Key Messages: The above findings suggest that Tau plays an essential role in mediating the neurodegenerative effects of stress and GCs towards the development of AD pathology. In addition, they highlight the involvement of Tau missorting in mechanism(s) of synaptic atrophy, beyond AD adding to our limited knowledge of the mechanisms through which stress causes brain pathology.
    Neurodegenerative Diseases 11/2015; DOI:10.1159/000440844
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    ABSTRACT: In recent years, tau immunotherapy has advanced from proof-of-concept studies [Sigurdsson EM, NIH R01AG020197, 2001; Asuni AA, et al: J Neurosci 2007;27:9115-9129], which have now been confirmed and extended by us and others. Phase I clinical trials on active and passive tau immunizations are being conducted, with several additional passive tau antibody trials likely to be initiated in the near future for Alzheimer's disease and other tauopathies. Because tau pathology correlates better with the degree of dementia than amyloid-β (Aβ) pathology, greater clinical efficacy may be achieved by clearing tau than Aβ aggregates in the later stages of the disease, when cognitive impairments become evident. Substantial insight has now been obtained regarding which epitopes to target, mechanism of action and potential toxicity, but much remains to be clarified. All of these factors likely depend on the model/disease or stage of pathology and the immunogen/antibody. Interestingly, tau antibodies interact with the protein both extra- and intracellularly, but the importance of each site for tau clearance is not well defined. Some antibodies are readily taken up into neurons, whereas others are not. It can be argued that extracellular clearance may be safer but less efficacious than intraneuronal clearance and/or sequestration to prevent secretion and further spread of tau pathology. Development of therapeutic tau antibodies has led to antibody-derived imaging probes, which are more specific than the dye-based compounds that are already in clinical trials. Such specificity may give valuable information on the pathological tau epitope profile, which could then guide the selection of therapeutic antibodies for maximal efficacy and safety. Hopefully, tau immunotherapy will be effective in clinical trials, and further advanced by mechanistic clarification in experimental models with insights from biomarkers and postmortem analyses of clinical subjects.
    Neurodegenerative Diseases 11/2015; DOI:10.1159/000440842
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    ABSTRACT: Background: Late-onset Alzheimer's disease is a genetically complex disorder. For 17 years, APOE was the only known susceptibility gene for disease. Through mostly genome-wide association studies, 25 loci are now known to associate with late-onset Alzheimer's disease. These susceptibility loci are not randomly distributed with respect to their functions. In fact, pathway analysis implicates significant enrichment of immunity, endocytosis, cholesterol metabolism, and ubiquitination in disease. Summary: Twenty-five loci have now been reliably shown to associate with Alzheimer's disease. However, a significant proportion of genetic variation in disease pathology is yet to be detected. Rare variation is being investigated through exome chip and next-generation sequencing experiments, which have already identified new protective and risk variants. Using a polygenic risk score approach, it is now possible to identify population groups with the greatest and fewest biological susceptibilities to disease. This method has proved more effective in predicting disease status than individual, genome-wide significant variants of small/moderate effect. Future studies will establish the specific functional changes that contribute to disease by piloting novel cellular modelling techniques using reprogrammed induced pluripotent stem cells from individuals with selected risk profiles. This will allow a variety of models to be produced to help understand disease mechanisms and test new drug therapies. Key Messages: Alzheimer's disease is a polygenic trait that has been linked to deficits in immunity, endocytosis, cholesterol metabolism and ubiquitination. Future work will focus on identifying rare disease susceptibility loci, unpicking the functional significance of the known risk loci and piloting novel cellular modelling techniques.
    Neurodegenerative Diseases 11/2015; DOI:10.1159/000440841
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    ABSTRACT: Background/aims: Recent studies have indicated a link between the impaired capacity of de novo protein synthesis and neurodegenerative diseases including Alzheimer's disease (AD). Moreover, it has been established that eukaryotic elongation factor 1A (eEF1A) plays a critical role in maintaining long-term synaptic plasticity, a cellular model for learning and memory. The aim of the present study is to determine whether brain eEF1A protein levels are dysregulated in brain tissue from AD patients compared with controls. Methods: Postmortem human brain samples collected from patients clinically diagnosed as AD, and from age-matched healthy controls, were utilized for this study. Both Western blot and immunohistochemistry approaches were utilized to investigate the potential alteration of eEF1A protein levels by using a specific antibody. Results: Our data demonstrate that eEF1A expression is reduced in AD patients in the hippocampus, but not in the cerebellum or midfrontal gyrus. Furthermore, immunohistochemical experiments reveal that neuronal eEF1A reduction in the AD hippocampus is localized to the CA1 and dentate gyrus, but not to the CA3. Conclusion: Dysregulation of eEF1A and its associated signaling pathways might represent novel molecular mechanisms underlying AD pathogenesis. Further investigation is necessary to determine whether eEF1A is a viable therapeutic target for AD and other cognitive syndromes.
    Neurodegenerative Diseases 11/2015; DOI:10.1159/000438925
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    ABSTRACT: The behavioral variant of frontotemporal dementia (bvFTD) is a neurodegenerative disease affecting people in their early sixties, characterized by dramatic changes in individual and social behavior. Despite the heterogeneity in the presentation of the clinical symptoms of bvFTD, some characteristic changes can be highlighted. Social disinhibition, changes in food preferences as well as loss of empathy and apathy are commonly described. This is accompanied by a characteristic and dramatic atrophy of the prefrontal cortex with the accumulation of protein aggregates in the neurons in this area. Several causative mutations in different genes have been discovered, allowing the development of transgenic animal models, especially mouse models. In mice, attention has been focused on the histopathological aspects of the pathology, but now studies are taking interest in assessing the behavioral phenotype of FTD models. Finding the right test corresponding to human symptoms is quite challenging, especially since the frontal cortex is much less developed in mice than in humans. Although challenging, the ability to detect relevant prefrontal cortex impairments in mice is crucial for therapeutic approaches. In this review, we aim to present the approaches that have been used to model the behavioral symptoms of FTD and to explore other relevant approaches to assess behavior involving the prefrontal cortex, as well as the deficits associated with FTD.
    Neurodegenerative Diseases 10/2015; DOI:10.1159/000439253
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    ABSTRACT: Aberrant accumulation of protein aggregates is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although a buildup of protein aggregates frequently leads to cell death, whether it is the key pathogenic factor in driving neurodegenerative disease remains controversial. HDAC6, a cytosolic ubiquitin-binding deacetylase, has emerged as an important regulator of ubiquitin-dependent quality control autophagy, a lysosome-dependent degradative system responsible for the disposal of misfolded protein aggregates and damaged organelles. Here, we show that in cell models HDAC6 plays a protective role against multiple disease-associated and aggregation-prone cytosolic proteins by facilitating their degradation. We further show that HDAC6 is required for efficient localization of lysosomes to protein aggregates, indicating that lysosome targeting to autophagic substrates is regulated. Supporting a critical role of HDAC6 in protein aggregate disposal in vivo, genetic ablation of HDAC6 in a transgenic SOD1G93A mouse, a model of ALS, leads to dramatic accumulation of ubiquitinated SOD1G93A protein aggregates. Surprisingly, despite a robust buildup of SOD1G93A aggregates, deletion of HDAC6 only moderately modified the motor phenotypes. These findings indicate that SOD1G93A aggregation is not the only determining factor to drive neurodegeneration in ALS, and that HDAC6 likely modulates neurodegeneration through additional mechanisms beyond protein aggregate clearance.
    Neurodegenerative Diseases 09/2015; DOI:10.1159/000437208
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    ABSTRACT: Leukoaraiosis (LA) patients may suffer from sensorimotor dysfunctions. The relationship between behavioral disturbances and changes in the sensorimotor network (SMN) has not been thoroughly elucidated. This study investigated the hypothesized breakdown of communication of SMN and its behavioral consequences in LA. Fluid-attenuated inversion recovery (FLAIR) images, resting-state functional magnetic resonance images (fMRI) and behavioral data were collected from 30 LA patients and 26 healthy individuals (normal controls, NC). The subjects were grouped according to LA severity, as indicated by their FLAIR images. Group independent component analysis was applied to the fMRI data to map the functional connectivity of SMN for NC and LA patients. A whole-brain, voxel-wise analysis was employed to investigate the functional connectivity alteration of SMN in LA. The relationships between LA severity, functional connectivity alteration of the SMN and behavioral clinical symptoms were examined by correlation analysis. The right cingulate motor area (rCMA), left posterior insula and left ventral premotor area showed attenuated functional connectivity in the LA patients. The extent of the attenuation was related to the severity of the disease. Furthermore, the attenuation in the rCMA was associated with worse sensorimotor integration performance. These results suggest that LA impairs sensorimotor integration by interfering with the communication or coordination of these aforementioned regions related to the SMN. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 08/2015; DOI:10.1159/000435918
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    ABSTRACT: Neurodegenerative diseases include a significant number of pathologies affecting the nervous system. Generally, the primary cause of each disease is specific; however, recently, it was shown that they may be correlated at molecular level. This aspect, together with the exhibition of similar symptoms, renders the diagnosis of these disorders difficult. Amyotrophic lateral sclerosis is one of these pathologies. Herein, we report several cases of amyotrophic lateral sclerosis misdiagnosed as a consequence of features that are common to several neurodegenerative diseases, such as Parkinson's, Huntington's and Alzheimer's disease, spinal muscular atrophy, progressive bulbar palsy, spastic paraplegia and frontotemporal dementia, and mostly with the lysosomal storage disorder GM2 gangliosidosis. Overall reports highlight that the differential diagnosis for amyotrophic lateral sclerosis should include correlated mechanisms. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; DOI:10.1159/000435917
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    ABSTRACT: Glucocerebrosidase (GBA) mutations have been described as the most prevalent in Parkinson's disease (PD) and in Lewy body dementia, accounting for up to 7 and 13.8% of cases, respectively. To elucidate the pathophysiology of idiopathic Parkinson's disease (iPD), the pathogenic mechanisms leading to Lewy body accumulation in GBA-associated parkinsonism (GBA-PD) are a matter of current research. However, only few imaging studies, conducted on small GBA-PD patient cohorts, exist. We provide an overview of current structural and functional imaging studies in patients with Gaucher's disease and parkinsonism and in GBA-PD patients, underlining the main differences compared to iPD. A limited number of PET studies have been conducted in GBA-PD, exploring brain metabolism and dopaminergic presynaptic and postsynaptic function. Moreover, structural MRI and spectroscopy studies recently evidenced the differences with iPD, aiding to understand of some peculiar aspects of iPD. Finally, new evidence from transcranial sonography confirms the technique's role in the study of GBA-PD and highlights the additional involvement of the raphe nucleus. Further imaging studies conducted in a broader population of early GBA-PD are warranted to characterize the disease and elucidate the pathophysiological mechanisms underlying GBA-PD and to understand GBA implications in iPD. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000433438
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    ABSTRACT: Previous studies indicate that patients with the parkinsonian subtype of multiple system atrophy (MSA-P) experience cognitive impairment. This study aimed to identify the existence of cognitive impairments and the different topographic patterns of morphological changes in MSA-P by means of imaging analysis, and also whether these morphological changes could be associated with cognitive dysfunctions in MSA-P. We recruited 15 nondemented probable MSA-P patients and 32 normal controls (NC) for neuropsychological testing and MRI. We analyzed morphological changes using cortical thickness analysis, voxel-based morphometry (VBM) and cerebellar volumetry. Multiple linear regression analysis was performed to evaluate the correlation of each cognitive score with the mean thickness of significant cortical-thinning clusters, mean gray-matter density of VBM clusters and cerebellar volume. The scores on the Digit Span Test, the Seoul Verbal Learning Test (immediate and delayed), the phonemic Controlled Oral Word Association Test and the Stroop color test were significantly lower in the MSA-P group than in the NC group. We found two clusters exhibiting significant cortical thinning in the right paracentral lobule and parahippocampal gyrus. VBM analysis revealed significant gray-matter atrophy in the MSA-P group in the bilateral basal ganglia, cerebellum and temporal and frontal cortical areas. Multiple linear regression analysis demonstrated that cognitive dysfunction correlated significantly with thinning in the neocortex, cerebellum and striatum. Our data demonstrate that cortical and cerebellar atrophy and striatal degeneration are associated with cognitive impairment in patients with MSA-P. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000430953
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    ABSTRACT: Alzheimer's disease (AD) is the most common disease causing neurodegeneration. The lower concentration of β-amyloid 1-42 (Aβ1-42) together with increased levels of total tau protein (T-tau) and phosphorylated tau protein (P-tau) in the cerebrospinal fluid (CSF) make a panel of well-established biomarkers in AD diagnosis. Addition of novel biomarkers to the gold standard biomarker panel might improve the diagnostic accuracy of neurodegeneration. This goal might be reached by the use of multiplexing, which is a simultaneous measurement of multiple analytes in a single sample volume and within a single cycle or run. Therefore the aim of the current review was to present, according to our best knowledge, available data concerning the evaluation of concentrations and diagnostic accuracy of well-established biomarkers in AD as well as novel biomarkers analyzed with the use of the bead-based technique. Additionally we discuss the utilization of the bead-based technique as compared to the conventional ELISA method. Literature data indicate that the bead-based technique revealed diagnostic sensitivity, specificity and coefficients of variation at the levels similar to ELISA. Moreover, an addition of novel biomarkers (tested by means of the bead-based technique) to the gold standard biomarker panel improved the diagnostic accuracy of neurodegeneration. Review of literature data shows that the combined analysis of classical CSF biomarkers with novel biomarkers might increase the specificity and sensitivity of performed tests. However, we concluded that the replacement of conventional ELISA with the bead-based technique requires new reference intervals for Aβ1-42, T-tau and P-tau concentrations. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000433439
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    ABSTRACT: Recent studies have suggested overlapping pathological features among motor neuron, cognitive and neurodegenerative diseases. Secondary analysis of 46 amyotrophic lateral sclerosis (ALS) patient autopsies was performed to independently assess pathological feature prevalence (e.g. percent of patients with any positive finding), degree of severity (e.g. mild, moderate, severe), and 2,200+ potential clinical/neuropathological correlations. The possible impact of gender, onset age, onset type (limb vs. bulbar), riluzole treatment, and severe TDP-43 pathology was assessed within patient subgroups. Assessed features (prevalence, severity) include: lateral corticospinal tract degeneration (89%, moderate); Purkinje cell loss (85%, mild); localized neuronal loss (83%, mild to moderate); TDP-43 inclusions (80%, moderate); Betz cell loss (76%, mild); neurofibrillary tangles (78%, severe); anterior corticospinal tract degeneration (72%, moderate); spinal ventral root atrophy (65%, moderate); atherosclerosis (35%, mild); β-amyloid (35%, mild); tauopathy/tau inclusions (17%, mild); ventricular dilation (13%, mild); Lewy body formation (11%, mild); microinfarcts (7%, mild); and α-synuclein (4%, mild). Twenty-two percent of patients met criteria for Alzheimer's disease (AD) and 26% for frontotemporal lobar degeneration. Substantial differences were identified in the AD group and in the different onset age groups. Our findings support the hypothesis that ALS and its variants could comprise a larger neuropathological continuum. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000433581
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    ABSTRACT: Parkin biology has emerged as an exciting area of pharmaceutical development for several human diseases, including cancer and neurodegeneration. Parkin's role is multifaceted in human health and disease and its function affecting major cellular quality control mechanisms, including the ubiquitin-proteasome and autophagy-lysosome systems, is critical in the maintenance of cellular homeostasis. Loss of Parkin function due to aging, protein instability and gene mutations is manifest in a number of human diseases, contributing to the validation of this protein as a therapeutic target. Parkin activation to mobilize cellular quality control mechanisms and counteract dyshomeostasis is a highly desirable area for therapeutic development. The elucidation of Parkin's crystal structure and better understanding of possible posttranslational modifications (i.e. phosphorylation, ubiquitination, etc.) that regulate Parkin's enzymatic activity suggest that this protein is a therapeutic drug target in many human diseases. Here we review Parkin's role in health and disease and discuss the effects of self-ubiquitination and deubiquitination on Parkin activity. This review provides further evidence showing the longitudinal effects of Parkin deletion on mitochondrial function, oxidative stress and neurotransmitter balance in vivo using high-frequency (1)H/(13)C NMR spectroscopy. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000430888