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)

In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders involving mitochondria can be divided into those caused by oxidative phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA) abnormalities, e.g., chronic external ophthalmoplegia, or due to nuclear mutations of OXPHOS proteins, e.g., complex I and II associated with Leigh syndrome. There are diseases caused by nuclear genes encoding non-OXPHOS mitochondrial proteins, such as frataxin in Friedreich ataxia (which is likely to play an important role in mitochondrial-cytosolic iron cycling), paraplegin (possibly a mitochondrial ATP-dependent zinc metalloprotease of the AAA-ATPases in hereditary spastic paraparesis), and possibly Wilson disease protein (an abnormal copper transporting ATP-dependent P-type ATPase associated with Wilson disease). Huntingon disease is an example of diseases with OXPHOS defects associated with mutations of nuclear genes encoding non-mitochondrial proteins such as huntingtin. There are also disorders with evidence of mitochondrial involvement that cannot as yet be assigned. These include Parkinson disease (where a complex I defect is described and free radicals are generated from dopamine metabolism), amyotrophic lateral sclerosis, and Alzheimer disease, where there is evidence to suggest mitochondrial involvement perhaps secondary to other abnormalities.
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PMID:Mitochondria and degenerative disorders. 1157 22

This review is designed to provide practical help for the clinical neurologist to make appropriate use of the possibilities of molecular diagnosis of inherited movement disorders. Huntington's disease, Parkinson's disease and parkinsonian syndromes, ataxias, Wilson disease, essential tremor, dystonias, and other genetic diseases associated with a variety of movement disorders are considered separately.
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PMID:State of the art review: molecular diagnosis of inherited movement disorders. Movement Disorders Society task force on molecular diagnosis. 1251 96

In this study, the focus is on midbrain magnetic resonance imaging morphometric measures (transverse diameter of the midbrain peduncle [Tp], transverse diameter of the tegmentum, anteroposterior diameter of the midbrain, interpeduncular distance [IPD], and interpeduncular angle [IPA]) in a group of 47 consecutive patients with neurologic (37 patients) and hepatic (10 patients) forms of Wilson disease (WD). Morphometric measures were significantly different between the group of patients with WD and healthy controls (51 subjects) as well as patients with Parkinson disease (15 patients) and multiple sclerosis (15 patients). Among the studied variables, IPA, Tp, and IPD were particularly useful in differentiating patients from healthy subjects (probability reaching 93%).
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PMID:Magnetic resonance imaging morphometry of the midbrain in patients with Wilson disease. 1627 67

Irving S. Cooper was a pioneer in the field of functional neurosurgery. During his very productive and controversial career, he proposed the surgical treatment of Parkinson disease (PD) by ligating the anterior choroidal artery to control tremor and rigidity. Subsequently, he developed seminal techniques for chemopallidectomy and cryothalamectomy for PD. He also attempted to use electrical stimulation of the cerebellum or the thalamus to treat spasticity. Cooper continued his work on brain stimulation until his death in 1985. He made video recordings of nearly all of his patients during his tenure (1977-1985) at New York Medical College. Cooper's clinical video recordings were reviewed, and selected footage was compiled into a video history of Cooper's surgical management of various movement disorders. Included are pre-, post-, and some intraoperative recordings that Cooper made to document his treatment of patients with PD, tremor, Wilson disease, cerebral palsy, chorea, dystonia musculorum deformans, and some rarer entities.
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PMID:Irving S. Cooper and the early surgical management of movement disorders. Video history. 1660 79

In MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-hydroxydopamine induced dopaminergic neurotoxicity and Parkinson's disease iron accumulates in substantia nigra pars compacta which has been suggested to participate in oxidative stress induced neurodegeneration. Pretreatment with iron chelators desferal, clioquinol, VK-28 and M30 are neuroprotective in both models. To determine the specificity of chelation neuroprotective activity we have examined the effect of D-penicillamine, a relatively specific copper chelator, in the mice model of MPTP-induced dopamine depletion. Our studies show that D-penicillamine, employed for removal of copper in Wilson disease is relatively weak in preventing dopaminergic neurotoxicity induced by MPTP, as compared to iron chelators previously studied. The results indicate that for prevention of MPTP-induced dopamine depletion and dopamine neurodegeneration, iron rather than copper chelation may be more effective and specific.
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PMID:The copper chelator, D-penicillamine, does not attenuate MPTP induced dopamine depletion in mice. 1673 32

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

Abnormal involuntary movements are major features of a large group of neurologic disorders, some of which are neurodegenerative and pose a significant diagnostic and treatment challenge to treating physicians. This article presents a concise review of clinical features, pathogenesis, epidemiology, and management of seven of the most common movement disorders encountered in a primary care clinic routinely. The disorders discussed are Parkinson disease, essential tremor, restless legs syndrome, Huntington disease, drug-induced movement disorder, Wilson disease, and Tourette syndrome.
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PMID:Movement disorders. 1927 14

Transcranial sonography is a highly sensitive noninvasive sonographic method for detection of early and specific echogenic changes in basal ganglia of patients with some neurodegenerative diseases. Transcranial sonography showed substantia nigra hyperechogenicity as a typical echo feature in idiopathic Parkinson disease and lenticular nucleus hyperechogenicity as a characteristic finding in atypical parkinsonian syndromes. Brain stem raphe hypoechogenicity or interruption has been shown to be highly prevalent in patients with unipolar depression as well as depression associated with certain neurodegenerative diseases. Transcranial sonography also revealed basal ganglia hyperechoic changes in movement disorders with trace metal accumulation such as Wilson disease, some entities of neurodegeneration with brain iron accumulation, as well as several forms of spinocerebellar ataxia. Transcranial sonography is a valuable neuro imaging method for early and differential diagnosis and follow-up of patients with neurodegenerative and psychiatric diseases.
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PMID:Transcranial brain parenchymal sonography in neurodegenerative and psychiatric diseases. 2542 61

Copper is an essential metal ion that provides catalytic function to numerous enzymes and also regulates neurotransmission and intracellular signaling. Conversely, a deficiency or excess of copper can cause chronic disease in humans. Menkes and Wilson disease are two rare heritable disorders of copper transport that are characterized by copper deficiency and copper overload, respectively. Changes to copper status are also a common feature of several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). In the case of AD, which is characterized by brain copper depletion, changes in the distribution of copper has been linked with various aspects of the disease process; protein aggregation, defective protein degradation, oxidative stress, inflammation and mitochondrial dysfunction. Although AD is a multifactorial disease that is likely caused by a breakdown in multiple cellular pathways, copper and other metal ions such as iron and zinc play a central role in many of these cellular processes. Pioneering work by researchers who have studied relatively rare copper transport diseases has shed light on potential metal ion related disease mechanisms in other forms of neurodegeneration such as AD.
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PMID:Metallo-pathways to Alzheimer's disease: lessons from genetic disorders of copper trafficking. 2739 42

Numerous causes may induce parkinsonism, and in case of Parkinsonism, l-dopa resistance, associated neurological signs, early falls, early dysautonomia or early cognitive disorders are the main red flags which should lead to exclude Parkinson's disease. Drug-induced parkinsonism and in young people, Wilson disease, should always be searched. Lower limbs parkinsonism is often due to vascular lesions. Multiple systemic atrophy, supranuclear palsy, Lewy body disease and the rarer corticobasal degeneration, each have specific clinical signs. Genetic causes are rarer.
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PMID:[Other causes of parkinsonism]. 2812 6


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