Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inherited movement disorders comprise a rapidly growing category of human disease. Advances in genetics have led to the identification of the gene mutation in Huntington's disease and three different gene mutations, which may lead to Parkinson's disease. In addition, gene mutations have been identified in less common movement disorders including Wilson's disease, Hallervorden-Spatz syndrome, paroxysmal kinesogenic choreoathetosis, neuroacanthocytosis, and some forms of dystonia. This article summarizes what is known about the genetic mutations that cause these movement disorders, as well as the clinical features of each disease and the symptomatic treatments currently available.
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PMID:Inherited movement disorders. 1243 29

STN-HFS is well known to improve patients with IPD. Because off-period dystonia mimics focal or generalized dystonia of other causes, we proposed bilateral STN-HFS to some patients with generalized dystonia. The aim of this study was to compare the efficacy of STN stimulation on off-period dystonia and generalized dystonia. From a larger series of patients with IPD, we selected 22 patients based on the presence of severe preoperative off-period dystonia rated > or = 3 in least one limb on a severity score ranging from 0 to 4. Four patients with generalized dystonia (Hallervorden-Spatz disease, n = 3; primary, n = 1) underwent bilateral STN-HFS. Dystonia of the four limbs was rated on video recordings in all patients before surgery and 3 months after surgery. In IPD, bilateral STN stimulation reduced the severity of off-period dystonia by 70% on the four limbs (preoperative mean severity score = 2.03 +/- 1.49; postoperative mean severity score = 0.60 +/- 0.78). In contrast, bilateral STN-HFS had no effect on generalized dystonia (preoperative mean severity score = 3.25 +/- 0.77; postoperative mean severity score = 3.12 +/- 0.62). Despite clinical similarities between off-period dystonia in Parkinson's disease and generalized dystonia in certain cases, the effect of chronic bilateral STN-HFS differs. STN stimulation is highly effective in off-period dystonia of IPD, whereas it does not improve generalized dystonia. The pathophysiologic mechanisms underlying dystonia in these two disorders are still unknown. Assuming that the mechanism of action of STN-HFS is similar regardless of the cause of dystonia, our findings suggest that the STN is not similarly involved in off-period dystonia of IPD and others dystonias.
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PMID:Off-period dystonia in Parkinson's disease but not generalized dystonia is improved by high-frequency stimulation of the subthalamic nucleus. 1450 88

Mutations in the pantothenate kinase 2 gene (PANK2) lead to pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome). This neurodegenerative disorder is characterized by iron accumulation in the basal ganglia. Pantothenate kinase is the first enzyme in the biosynthesis of coenzyme A from pantothenate (vitamin B(5)). PANK2, one of four human pantothenate kinase genes, is uniquely predicted to be targeted to mitochondria. We demonstrate mitochondrial localization of PANK2 and speculate on mechanisms of secondary iron accumulation in PKAN. Furthermore, PANK2 uses an unconventional translational start codon, CUG, which is polymorphic in the general population. The variant sequence, CAG (allele frequency: 0.05), leads to skipping of the mitochondrial targeting signal and cytosolic localization of PANK2. This common variant may cause mitochondrial dysfunction and impart susceptibility to late-onset neurodegenerative disorders with brain iron accumulation, including Parkinson's disease.
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PMID:Mitochondrial localization of human PANK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration. 1510 73

For the last century, there has been great physiological interest in brain iron and its role in brain function and disease. It is well known that iron accumulates in the brain for people with Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, chronic hemorrhage, cerebral infarction, anemia, thalassemia, hemochromatosis, Hallervorden-Spatz, Down syndrome, AIDS and in the eye for people with macular degeneration. Measuring the amount of nonheme iron in the body may well lead to not only a better understanding of the disease progression but an ability to predict outcome. As there are many forms of iron in the brain, separating them and quantifying each type have been a major challenge. In this review, we present our understanding of attempts to measure brain iron and the potential of doing so with magnetic resonance imaging. Specifically, we examine the response of the magnetic resonance visible iron in tissue that produces signal changes in both magnitude and phase images. These images seem to correlate with brain iron content, perhaps ferritin specifically, but still have not been successfully exploited to accurately and precisely quantify brain iron. For future quantitative studies of iron content we propose four methods: correlating R2' and phase to iron content; applying a special filter to the phase to obtain a susceptibility map; using complex analysis to extract the product of susceptibility and volume content of the susceptibility source; and using early and late echo information to separately predict susceptibility and volume content.
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PMID:Imaging iron stores in the brain using magnetic resonance imaging. 1573 84

Alpha-synuclein is a presynaptic protein which is implicated in some neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies, multiple systems atrophy, and Hallervorden-Spatz disease, and its overexpression contributes to the loss of dopaminergic neurons. Although the role of alpha-synuclein in these paradigms has been widely documented, its exact function is still elusive. And the dysfunction of the transcription factor nuclear factor (NF-kappaB) also exists in many neurodegenerative diseases. In this reason the purpose of this study was to investigate the molecular mechanism of alpha-synuclein's toxicity and its association with NF-kappaB by MTT assay, Western blot method, and luciferase assay. Results showed that overexpressed alpha-synuclein and 1-methyl-4-phenylpyridinium (MPP(+)) suppressed the SH-SY5Y cell viability and attenuate NF-kappaB-mediated luciferase expression significantly. Moreover, the impairment function was enhanced with the increase of alpha-synuclein protein level. We also found that overexpressed alpha-synuclein localized both in the cytoplasms and nuclei, down-regulated the anti-apoptotic Bcl-2 expression and up-regulated the pro-apoptotic glycogen synthase kinase 3beta (GSK3beta) protein level. In conclusion, all these findings mentioned above suggested that alpha-synuclein shared some toxic functional homology with neurotoxin MPP(+), and the proapoptotic effects of alpha-synuclein might be mediated at least in part by the impairment of NF-kappaB signaling pathway which involves GSK3beta.
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PMID:Overexpressed alpha-synuclein regulated the nuclear factor-kappaB signal pathway. 1771 23

Frontal-subcortical dementias are a heterogeneous group of disorders that share primary pathology in subcortical structure and a characteristic pattern of neuropsychologic impairment. Their clinical presentation is characterized by memory disorders, an impaired ability to manipulate acquired knowledge, important changes of personality (apathy, inertia, or depression), and slowed thought processes (or bradyphrenia). It also has marked frontal dysfunction. Classic frontal-subcortical dementias include Huntington chorea, Parkinson disease dementia, progressive supranuclear palsy, thalamic degeneration, subcortical vascular dementia, multiple sclerosis, the acquired immunodeficiency syndrome dementia complex, depressive pseudodementia, and some other rare dementias like spinocerebellar degenerative syndromes, Hallervorden-Spatz disease, choreoacanthocytosis, idiopathic basal ganglia calcification, Guamanian parkinsonism-dementia complex, corticobasal degeneration multiple system atrophy, Wilson disease, metachromatic leukodystrophy, adrenoleukodystrophy, hypoparathyroidism, sarcoidosis, and other CNS inflammatory disorders. Anatomic data suggest that the frontal signs result from a disconnection of the frontal cortex from the basal ganglia. However, most frontal-subcortical dementias show cortical atrophy in later stages, and cortical dementias have subcortical pathology at some point. In fact, the concept might be seen as a continuum, and only the 2 extremes would be represented by pure cortical or subcortical pathology. Anyway, subcortical disorders may still be more similar to one another than they are to AD. Possibly, frontal-subcortical and cortical dementias are the description of the prior main target of the disease process, ending up in both cases in a global dementia. Although the dichotomy cortical versus frontal-subcortical dementia is not strict, the 2 concepts still seem to have advantages.
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PMID:Frontal-subcortical dementias. 1833 39

Alzheimer's disease (AD) is a devastating neuro-degenerative disorder characterized by the progressive and irreversible loss of memory followed by complete dementia. Despite the disease's high prevalence and great economic and social burden, an explicative etiology or viable cure is not available. Great effort has been made to better understand the disease's pathogenesis, and to develop more effective therapeutic agents. However, success is greatly hampered by the presence of the blood-brain barrier that limits a large number of potential therapeutics from entering the brain. Nanoparticle-mediated drug delivery is one of the few valuable tools for overcoming this impediment and its application as a potential AD treatment shows promise. In this review, the current studies on nanoparticle delivery of chelation agents as possible therapeutics for AD are discussed because several metals are found excessive in the AD brain and may play a role in the disease development. Specifically, a novel approach involving transport of iron chelation agents into and out of the brain by nanoparticles is highlighted. This approach may provide a safer and more effective means of simultaneously reducing several toxic metals in the AD brain. It may also provide insights into the mechanisms of AD pathophysiology, and prove useful in treating other iron-associated neurodegenerative diseases such as Friedreich's ataxia, Parkinson's disease, Huntington's disease and Hallervorden-Spatz Syndrome. It is important to note that the use of nanoparticle-mediated transport to facilitate toxicant excretion from diseased sites in the body may advance nanoparticle technology, which is currently focused on targeted drug delivery for disease prevention and treatment. The application of nanoparticle-mediated drug transport in the treatment of AD is at its very early stages of development and, therefore, more studies are warranted.
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PMID:Metal chelators coupled with nanoparticles as potential therapeutic agents for Alzheimer's disease. 1993 78

Magnetic resonance imaging (MRI) is frequently used in the evaluation of various extrapyramidal disorders. Among the plethora of MRI features in Wilson's disease (WD), only "face of the giant panda" sign has been recognized to distinguish WD from other early onset extrapyramidal disorders (EOEPD). To ascertain the value of various MRI features in differentiating neuropsychiatric form of WD from other EOEPD. This retrospective analysis included 100 patients (M:F = 56:44) of EOEPD (5-40 years), who had undergone MRI during Jan'03 to Nov'08. Their clinical features were recorded and the following MR sequences were analyzed: T1WI, T2WI, FLAIR. Fifty-six patients had WD (M:F = 28:30, age at onset: 14 +/- 6.8 years) and 44 had other EOEPD (M:F = 27:17, age at onset: 19 +/- 9.8 years) that included Huntington's disease--4, young-onset Parkinson's disease--7, mitochondrial disorders--2, Hallervorden-Spatz disease--8, non-Wilsonian hepatolenticular degeneration--2, toxic/metabolic disorder--1, and others--20. The duration of illness at the time of MRI was comparable (WD: 3.1 +/- 4.9 years; Other EOEPD: 2.8 +/- 2.4 years). MR signal characteristics varied in topography and severity in both the groups. All the patients of WD had signal abnormalities in MRI, as against 16/44 of the other EOEPD group. The following MR observations were noted exclusively in WD: "Face of giant panda" sign (14.3%), tectal plate hyperintensity (75%), central pontine myelinolysis (CPM)-like abnormalities (62.5%), and concurrent signal changes in basal ganglia, thalamus, and brainstem (55.3%). Besides "Face of giant panda" sign, hyperintensities in tectal-plate and central pons (CPM-like), and simultaneous involvement of basal ganglia, thalamus, and brainstem are virtually pathognomonic of WD.
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PMID:Do MRI features distinguish Wilson's disease from other early onset extrapyramidal disorders? An analysis of 100 cases. 2043 36

In humans overlap between various neurodegenerative disorders is a well known phenomenon. We reported a case of a 77-year-old woman with parkinsonism, dystonia, psychiatric symptoms and progressing dementia misdiagnosed at the age of 51 years as Parkinson's disease. Histopathological examination of the patient's brain performed 26 years after the disease onset revealed numerous axonal spheroids and iron deposits in structures of the nigro-pallido-striatal system that enabled to diagnose neurodegeneration with brain iron accumulation (NBIA) (former Hallervorden-Spatz syndrome), and changes characteristic for Alzheimer's disease (AD). NBIA is a group of rare clinically and genetically heterogeneous diseases of the extrapyramidal system which common feature is abnormal iron storage in the basal ganglia. Disturbed iron metabolism is also one of the hypothetical patho-mechanisms of AD. A coexistence of morphological changes characteristic for AD and NBIA in our patient suggests that similar molecular mechanisms may be involved in pathogenesis of various neurodegenerative processes, especially in disorders with iron dyshomeostasis. This case contributes also to the increasing evidence of NBIA heterogeneity.
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PMID:Dementia means number of things - the overlap of neurodegeneration with brain iron accumulation (NBIA) and Alzheimer changes: an autopsy case. 2060 94

Seven autosomal recessive genes associated with juvenile and young-onset Levodopa-responsive parkinsonism have been identified. Mutations in PRKN, DJ-1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor-Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden-Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor-Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido-pyramidal syndrome.
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PMID:Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations. 2066 27


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