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Juvenile Parkinsonism (juvenile + parkinsonism)
Kinds of Juvenile Parkinsonism Selected AbstractsJuvenile Parkinsonism: a term in search of an identityEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2000J. W. Langston No abstract is available for this article. [source] Diagnostic considerations in juvenile parkinsonismMOVEMENT DISORDERS, Issue 2 2004Dominic C. Paviour MRCP Abstract Juvenile parkinsonism (JP) describes patients in whom the clinical features of parkinsonism manifest before 21 years of age. Many reported cases that had a good response to levodopa have proved to have autosomal recessive juvenile parkinsonism (AR-JP) due to mutations in the parkin gene. With the exception of parkin mutations and dopa-responsive dystonia, most causes are associated with the presence of additional neurological signs, resulting from additional lesions outside of the basal ganglia. Lewy body pathology has only been reported in one case, suggesting that a juvenile form of idiopathic Parkinson's disease may be extremely rare. © 2003 Movement Disorder Society [source] Identification and characterization of a novel endogenous murine parkin mutationJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Chenere P. Ramsey J. Neurochem. (2010) 113, 402,417. Abstract Various mutations in the PARK2 gene which encodes the protein, parkin, are causal of a disease entity-termed autosomal recessive juvenile parkinsonism. Parkin can function as an E3 ubiquitin-protein ligase, mediating the ubiquitination of specific targeted proteins and resulting in proteasomal degradation. Parkin is thought to lead to parkinsonism as a consequence of a loss in its function. In this study, immunoblot analyses of brain extracts from Balb/c, C57BL/6, C3H, and 129S mouse strains demonstrated significant variations in immunoreactivity with anti-parkin monoclonal antibodies (PRK8, PRK28, and PRK109). This resulted partly from differences in the steady-state levels of parkin protein across mouse strains. There was also a complete loss of immunoreactivity for PRK8 and PRK28 antibodies in C3H mice due to was because of a homologous nucleotide mutation resulting in an E398Q amino acid substitution. In cultured cells, parkin harboring this mutation had a greater tendency to aggregate, exhibited reduced interaction with the E2 ubiquitin-conjugating enzymes, UbcH7 and UbcH8, and demonstrated loss-of-function in promoting the proteosomal degradation of a specific putative substrate, synphilin-1. In situ, C3H mice displayed age-dependent increased levels of brain cortical synphilin-1 compared with C57BL/6, suggesting that E398Q parkin in these mice is functionally impaired and that C3H mice may be a suitable model of parkin loss-of-function similar to patients with missense mutations. [source] A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of ParkinJOURNAL OF NEUROCHEMISTRY, Issue 6 2006Tomohiro Omura Abstract It has been proposed that in autosomal recessive juvenile parkinsonism (AR-JP), a ubiquitin ligase (E3) Parkin, which is involved in endoplasmic reticulum-associated degradation (ERAD), lacks E3 activity. The resulting accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), a substrate of Parkin, leads to endoplasmic reticulum stress, causing neuronal death. We previously reported that human E3 HRD1 in the endoplasmic reticulum protects against endoplasmic reticulum stress-induced apoptosis. This study shows that HRD1 was expressed in substantia nigra pars compacta (SNC) dopaminergic neurons and interacted with Pael-R through the HRD1 proline-rich region, promoting the ubiquitylation and degradation of Pael-R. Furthermore, the disruption of endogenous HRD1 by small interfering RNA (siRNA) induced Pael-R accumulation and caspase-3 activation. We also found that ATF6 overexpression, which induced HRD1, accelerated and caused Pael-R degradation; the suppression of HRD1 expression by siRNA partially prevents this degradation. These results suggest that in addition to Parkin, HRD1 is also involved in the degradation of Pael-R. [source] Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations,MOVEMENT DISORDERS, Issue 13 2009Nadège Limousin MD Abstract Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35,60 years, from seven families) and 11 sex-matched patients with iPD (aged 51,65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent. © 2007 Movement Disorder Society [source] Chronic bilateral subthalamic deep brain stimulation in a patient with homozygous deletion in the Parkin geneMOVEMENT DISORDERS, Issue 12 2004Marianna Capecci MD Abstract Chronic subthalamic nucleus deep brain stimulation (STN-DBS) is an efficacious treatment for idiopathic Parkinson's disease (PD) that cannot be further improved by medical therapy. We present a case of an individual with juvenile parkinsonism caused by homozygous deletion of exon 3 in the parkin gene with disabling long-term side-effects from levodopa who underwent bilateral STN neuromodulation. Parkin-linked parkinsonism may show clinical features different from sporadic PD, yet it shares levodopa responsiveness. Because levodopa responsiveness is a predictor of STN-DBS efficacy, we argued that this kind of surgical approach might be efficacious in hereditary parkin-linked juvenile parkinsonism. We evaluated clinical and functional assessment before and 12 months after surgery. The results showed that the Unified Parkinson Disease Rating Scales Motor score improved by 84% in our patient, the levodopa equivalent daily dose medication (LEDD) was reduced by 66%, and, finally, disabling and severe dyskinesias disappeared. © 2004 Movement Disorder Society [source] Diagnostic considerations in juvenile parkinsonismMOVEMENT DISORDERS, Issue 2 2004Dominic C. Paviour MRCP Abstract Juvenile parkinsonism (JP) describes patients in whom the clinical features of parkinsonism manifest before 21 years of age. Many reported cases that had a good response to levodopa have proved to have autosomal recessive juvenile parkinsonism (AR-JP) due to mutations in the parkin gene. With the exception of parkin mutations and dopa-responsive dystonia, most causes are associated with the presence of additional neurological signs, resulting from additional lesions outside of the basal ganglia. Lewy body pathology has only been reported in one case, suggesting that a juvenile form of idiopathic Parkinson's disease may be extremely rare. © 2003 Movement Disorder Society [source] Involvement of spinal motor neurons in parkin-positive autosomal recessive juvenile parkinsonismNEUROPATHOLOGY, Issue 1 2008Shoichi Sasaki We intensively examined the spinal cord of an autosomal recessive juvenile parkinsonism (ARJP) female patient with a homozygous exon 3 deletion in the parkin gene, anticipating a possible involvement of anterior horn neurons. Although the clinical features of the patient were consistent with parkinsonism as a result of parkin mutation, her tendon reflex was abolished in the lower limbs. This feature was in contrast with hyperreflexia, usually found in previous reports of ARJP. Histologically, on the level of the cervical, thoracic, and sacral spinal cord, anterior horn neurons were well preserved and normal. However, the lumbar spinal cord exhibited many swellings of proximal axons (spheroids) and degenerative changes in the somata of the large anterior horn neurons such as central chromatolysis, cystatin C-negative small eosinophilic inclusions, and eosinophilic Lewy body-like inclusions. Ultrastructurally, accumulations of neurofilaments and abnormal structures, such as inclusion bodies similar to skein-like inclusions and disorganized rough endoplasmic reticulum, were observed in the somata and neuronal processes. Lewy body-like inclusions in this study were positively immunostained for both ,-synuclein and ubiquitin that closely resemble Lewy bodies, but are different from Lewy body-like inclusions negatively immunostained for ,-synuclein in amyotrophic lateral sclerosis. These findings suggest that eosinophilic inclusions that closely resemble Lewy bodies may be formed in the spinal motor neurons of ARJP patients with parkin mutations and the motor neurons of these patients may be vulnerable to neurodegeneration. [source] | ||||||||||