Parkinson syndrome as a manifestation of mitochondriopathy

Finsterer, Josef

doi:10.1034/j.1600-0404.2002.01221.x

Cited by 13 publications

(12 citation statements)

References 32 publications

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“…A parkinsonian syndrome was also associated with one of the LHON mutations in complex I. On the other hand, it was recently reported that about 10% of patients diagnosed with clinical, biochemical, and/or morphological features of mitochondrial disease had features of parkinsonism, and that these patients responded positively to anti-Parkinson medications (44). Unfortunately, however, none of the 76 patients studied were diagnosed at the genetic level.…”

Section: Parkinson Diseasementioning

confidence: 95%

Neuronal degeneration and mitochondrial dysfunction

Schon¹,

Manfredi²

2003

J. Clin. Invest.

264

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Over the last decade, the underlying genetic bases of several neurodegenerative disorders, including Huntington disease (HD), Friedreich ataxia, hereditary spastic paraplegia, and rare familial forms of Parkinson disease (PD), Alzheimer disease (AD), and amyotrophic lateral sclerosis (ALS), have been identified. However, the etiologies of sporadic AD, PD, and ALS, which are among the most common neurodegenerative diseases, are still unclear, as are the pathogenic mechanisms giving rise to the various, and often highly stereotypical, clinical features of these diseases. Despite the differential clinical features of the various neurodegenerative disorders, the fact that neurons are highly dependent on oxidative energy metabolism has suggested a unified pathogenetic mechanism of neurodegeneration, based on an underlying dysfunction in mitochondrial energy metabolism.Mitochondria are the seat of a number of important cellular functions, including essential pathways of intermediate metabolism, amino acid biosynthesis, fatty acid oxidation, steroid metabolism, and apoptosis. Of key importance to our discussion here is the role of mitochondria in oxidative energy metabolism. Oxidative phosphorylation (OXPHOS) generates most of the cell's ATP, and any impairment of the organelle's ability to produce energy can have catastrophic consequences, not only due to the primary loss of ATP, but also due to indirect impairment of "downstream" functions, such as the maintenance of organellar and cellular calcium homeostasis. Moreover, deficient mitochondrial metabolism may generate reactive oxygen species (ROS) that can wreak havoc in the cell. It is for these reasons that mitochondrial dysfunction is such an attractive candidate for an "executioner's" role in neuronal degeneration.The mitochondrion is the only organelle in the cell, aside from the nucleus, that contains its own genome and genetic machinery. The human mitochondrial genome (1) is a tiny 16.6-kb circle of double-stranded mitochondrial DNA (mtDNA) (Figure 1). It encodes 13 polypeptides, all of which are components of the respiratory chain/OXPHOS system, plus 24 genes, specifying two ribosomal RNAs (rRNAs) and 22 transfer RNAs (tRNAs), that are required to synthesize the 13 polypeptides. Obviously, an organelle as complex as a mitochondrion requires more than 37 gene products; in fact, about 850 polypeptides, all encoded by nuclear DNA (nDNA), are required to build and maintain a functioning organelle. These proteins are synthesized in the cytoplasm and are imported into the organelle, where they are partitioned into the mitochondrion's four main compartments -the outer mitochondrial membrane (OMM), the inner mitochondrial membrane (IMM), the intermembrane space (IMS), and the matrix, located in the interior (the organelle's "cytoplasm"). Of the 850 proteins, approximately 75 are structural components of the respiratory complexes ( Figure 2) and at least another 20 are required to assemble and maintain them in working order. The five complexes of the respiratory chain...

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Section: Parkinson Diseasementioning

confidence: 95%

Neuronal degeneration and mitochondrial dysfunction

Schon¹,

Manfredi²

2003

J. Clin. Invest.

264

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“…In a series of 76 adult patients with various mitochondrial disorders, Finsterer (2002) found 9 patients (12%) with parkinsonism. Parkinsonism has been observed in patients with polymerase gamma (POLG) and DNA helicase Twinkle gene mutations.…”

Section: Respiratory Chain Disorders (Rcds)mentioning

confidence: 98%

Movement disorders and inborn errors of metabolism in adults: A diagnostic approach

Sedel

Saudubray

Roze

et al. 2008

J of Inher Metab Disea

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Inborn errors of metabolism (IEMs) may present in adolescence or adulthood with various movement disorders including parkinsonism, dystonia, chorea, tics or myoclonus. Main diseases causing movement disorders are metal-storage diseases, neurotransmitter synthesis defects, energy metabolism disorders and lysosomal storage diseases. IEMs should not be missed as many are treatable. Here we briefly review IEMs causing movement disorders in adolescence and adults and propose a simple diagnostic approach to guide metabolic investigations based on the clinical course of symptoms, the type of abnormal movements, and brain MRI abnormalities.

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“…Finsterer 77 reported metabolic studies indicating that PD can be a manifestation of MCP. In his series, 6.3% of PD patients had features of generalized MCP; however, he used lactate stress testing to detect patients with MCP-an approach that could not be expected to pick up mitochondrial lesions limited to brain sites.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Ketones: Metabolism's Ugly Duckling

2003

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Ketones were first discovered in the urine of diabetic patients in the mid-19th century; for almost 50 years thereafter, they were thought to be abnormal and undesirable by-products of incomplete fat oxidation. In the early 20th century, however, they were recognized as normal circulating metabolites produced by liver and readily utilized by extrahepatic tissues. In the 1920s, a drastic "hyperketogenic" diet was found remarkably effective for treatment of drug-resistant epilepsy in children. In 1967, circulating ketones were discovered to replace glucose as the brain's major fuel during the marked hyperketonemia of prolonged fasting. Until then, the adult human brain was thought to be entirely dependent upon glucose. During the 1990s, diet-induced hyperketonemia was found therapeutically effective for treatment of several rare genetic disorders involving impaired neuronal utilization of glucose or its metabolic products. Finally, growing evidence suggests that mitochondrial dysfunction and reduced bioenergetic efficiency occur in brains of patients with Parkinson's disease (PD) and Alzheimer's disease (AD). Because ketones are efficiently used by mitochondria for ATP generation and may also help protect vulnerable neurons from free radical damage, hyperketogenic diets should be evaluated for ability to benefit patients with PD, AD, and certain other neurodegenerative disorders.

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Parkinson syndrome as a manifestation of mitochondriopathy

Abstract: Twelve per cent of the patients with MCP have phenotypic features of PS and 6% of the patients with PS have features of MCP. MCP patients with PS frequently show multisystem involvement. PS in MCP responds well to anti-Parkinson medication.

Cited by 13 publications

References 32 publications

Neuronal degeneration and mitochondrial dysfunction

Neuronal degeneration and mitochondrial dysfunction

Movement disorders and inborn errors of metabolism in adults: A diagnostic approach

Ketones: Metabolism's Ugly Duckling

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