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The main biochemical characteristic of Parkinson’s disease (PD) is reduction of the neurotransmitter dopamine and the dopamine-synthesizing enzyme system, including tyrosine hydroxylase (TH, tyrosine 3-monooxygenase, EC 1.14.16.2) and tetrahydrobiopterin (BH4 co-fac ...

Transcription regulation is a complex but key control mechanism that underlies differential gene expression during development and in the adult organism. Like all protein coding genes, those encoding dopamine receptors are subject to this form of regulation as well. Modifications ...

In situ hybridization (ISH) is an important method for determining the distribution of mRNA within cells or tissue preparations by hybridization of a nucleic acid probe (either DNA or RNA) with a specific target nucleic acid (usually mRNA) (1,2). Thus, ISH enables the localization of transcri ...

An emerging new technology based on genetic engineering of viral vectors that can insert genes into the cells of living organisms may play a significant role in treating disorders of the central nervous system (CNS). Most neurodegenerative disorders affect focal regions of the brain. Prev ...

The most common treatment for Parkinson’s disease (PD) aims at pharmacologically augmenting striatal dopamine (DA) using the DA precursor levodopa. Such treatment provides symptomatic relief, but does not slow or halt continued degeneration of nigral dopaminergic neurons. Cons ...

Mutation detection in an integral part of disease diagnosis and patient study. For most Mendelian diseases, multiple mutations may be found in a single gene among a patient population. The type of mutations may vary from large deletions to single-base-pair (bp) substitutions, and different ...

Cystic fibrosis (CF) is a single-gene disorder with a complex phenotype, in which multiple organs are affected. The pulmonary complications of CF, including mucous plugging and chronic bacterial infection of the lung, represent the major cause of morbidity and mortality (1). It has long been s ...

The earth’s organisms are a vast repository of genetic diversity. Each species (n106) is distinguished from every other by a unique genomic sequence that is passed on to successive generations with extremely high, but not perfect, fidelity. Imperfections in DNA replication and repair mean t ...

The cystic fibrosis transmembrane conductance regulator (CFTR) forms a chloride channel whose activation is regulated by phosphorylation and by ATP binding and hydrolysis (1-4). The functional properties of the channel have been extensively studied using electrophysiologi ...

CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) is a cAMP-activated chloride channel present on the apical surfaces of epithelial cells. This protein has been shown to be responsible for salt and water transport across epithelia (1). CFTR has been implicated in two major dis ...

Halide-sensitive fluorescent indicators have been useful in cystic fibrosis (CF) research in assaying functional cystic fibrosis transmembrane conductance regulator (CFTR) expression in cells. Some applications (for review, see refs. 1 and 2) have included measurements in na ...

Cloning of the cystic fibrosis (CF) gene provided, for the first time, the structural information needed to more precisely define the CF defect (1-3). This genetic information was used to develop powerful molecular and antibody reagents that helped define cystic fibrosis transmembrane c ...

Expression of endogenous cystic fibrosis transmembrane conductance regulator (CFTR) in many epithelial cells is either low or difficult to detect or below the limit of detection using currently available microscopic techniques (1,2). In addition, studies utilizing CFTR antibo ...

The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane glycoprotein that contains several large cytosolic subdomains. To progress through the secretory pathway, CFTR must fold and assemble its subdomains into stable conformations that permit exit from t ...

The most common cause of cystic fibrosis is the deletion of a phenylalanine at position 508 (gDF508) of the cystic fibrosis transmembrane conductance regulator (CFTR). Although the majority of wild-type CFTR is degraded in the endoplasmic reticulum (ER), suggesting that its folding effi ...

Defective protein folding is becoming increasingly recognized as a significant cause of human disease, and cystic fibrosis (CF) is a prime example. A number of CF-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) result in a CFTR protein that does not re ...

Defects in protein folding constitute the basis of many genetic diseases: cystic fibrosis, alpha-1 antitrypsin deficiency, familial hypercholesterolemia, and congenital nephrogenic diabetes insipidus, to name but a few (see Table 1 for a complete list). In each of these, point mutati ...

The regulated degradation of cellular proteins occurs primarily through the ATP-dependent ubiquitin/proteasome pathway (1). One function of this pathway is to control the quality of nascent proteins (2). In this process ubiquitinconjugating enzymes and ubiquitin-protein li ...

Cystic fibrosis (CF), a severe autosomal recessive disorder, is marked by reduced regulated chloride conductance across the apical membrane of affected epithelia. This reduction is attributable to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), w ...

Correct localization of cystic fibrosis transmembrane conductance regulator (CFTR) is critical to its function. Although an intracellular role for CFTR is still somewhat controversial (1), there is clear agreement on an important role for CFTR in the plasma membrane. However, it is not on ...