Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunohistochemical expression of the aspartyl protease enzyme cathepsin D was examined in a consecutive series of 103 primary operable breast carcinomas with the polyclonal antibody NCL-CDp. Expression of cathepsin D was identified within the epithelial and stromal components of all tumours examined. No significant associations of increased cathepsin D expression in the epithelial tumour component with conventional prognostic indices such as tumour size, grade, lymph node stage, or patient survival were identified. However, significant associations of increased stromal cathepsin D expression and high tumour grade, chi 2 = 11.40 (df = 2), p = 0.003; increased tendency to local recurrence, chi 2 = 6.87 (df = 1), p = 0.009; regional recurrence, chi 2 = 7.44 (df = 1), p = 0.006; poorer disease free survival, chi 2 = 14.9 (df = 1), p = 0.0001; and poorer overall patient survival, chi 2 = 6.90 (df = 1), p = 0.0086, were identified. Cathepsin D expression is present in all breast tumours. Stromal cathepsin D expression is a neglected immunohistochemical prognostic parameter which could explain some of the previous apparently conflicting reports concerning the effect on patient prognosis of biochemical (i.e. total) and immunohistochemical estimations of cathepsin D in breast cancers.
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PMID:Cathepsin D in primary breast carcinoma: adverse prognosis is associated with expression of cathepsin D in stromal cells. 774 41

We describe the neuropathological and biochemical autopsy findings in 3 patients with autosomal dominant adult neuronal ceroid lipofuscinosis (ANCL, Parry type; MIM 162350), from a family with 6 affected individuals in 3 generations. Throughout the brain of these patients, there was abundant intraneuronal lysosomal storage of autofluorescent lipopigment granules. Striking loss of neurons in the substantia nigra was found. In contrast, little neuronal cell loss occurred in other cerebral areas, despite massive neuronal inclusions. Visceral storage was present in gut, liver, cardiomyocytes, skeletal muscle, and in the skin eccrine glands. The storage material showed highly variable immunoreactivity with antiserum against subunit c of mitochondrial ATP synthase, but uniform strong immunoreactivity for saposin D (sphingolipid activating protein D). Protein electrophoresis of isolated storage material revealed a major protein band of about 14 kDa, recognized in Western blotting by saposin D antiserum (but not subunit c of mitochondrial ATPase (SCMAS) antiserum). Electron microscopy showed ample intraneuronal granular osmiophilic deposits (GRODs), as occurs in CLN1 and congenital ovine NCL. These forms of NCL are caused by the deficiencies of palmitoyl protein thioesterase 1 and cathepsin D, respectively. However, activities of these enzymes were within normal range in our patients. Thus we propose that a gene distinct from the cathepsin D and CLN1-CLN8 genes is responsible for this autosomal dominant form of ANCL.
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PMID:Autosomal dominant adult neuronal ceroid lipofuscinosis: a novel form of NCL with granular osmiophilic deposits without palmitoyl protein thioesterase 1 deficiency. 1465 61

Neuronal ceroid lipofuscinoses are a group of diseases characterized by accumulation of hydrophobic proteins in lysosomes of neurons and other types of cells. NCLs are caused by at least 8 mutant genes (CLN1-CLN8), though CLN4 and CLN7 have not yet been identified. Except for Cln1p, the protein encoded by CLN1, the defective proteins are associated with lysosomal accumulation of mitochondrial ATP synthase subunit c. Cln1p and Cln2p are soluble lysosomal enzymes, targeted to lysosomes in a mannose 6-phosphate dependent manner. Mutations in the lysosomal protease cathepsin D cause another NCL. Cln3p, Cln5p, Cln6p and Cln8p are thought to be transmembrane proteins. Cln3p and Cln5p are localized in the endosome-lysosomal compartment. Deficiency of endosomal membrane protein CLC-3, a member of the chloride channel family, causes NCL-like phenotype and lysosomal storage of subunit c. Herein, we review the features of NCL and NCL-related proteins and discuss the involvement of the proteins in lysosomal degradation of subunit c.
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PMID:The intracellular location and function of proteins of neuronal ceroid lipofuscinoses. 1499 40

The neuronal ceroid lipofuscinoses (NCL, also known as Batten disease) is a devastating neurodegenerative diseases caused by mutations in either soluble enzymes or membrane-associated structural proteins that result in lysosome dysfunction. Different forms of NCL were defined initially by age of onset, affected population and/or type of storage material but collectively represent the most prevalent pediatric hereditary neurovisceral storage disorder. Specific gene mutations are now known for each subclass of NCL in humans that now largely define the disease: cathepsin D (CTSD) for congenital (CLN10 form); palmitoyl protein thioesterase 1 (PPT1) for infantile (CLN1 form); tripeptidyl peptidase 1 (TPP1) for classic late infantile (CLN2 form); variant late infantile-CLN5, CLN6 or CLN8 for variant late infantile forms; and CLN3 for juvenile (CLN3 form). Several mouse models of NCL have been developed, or in some cases exist sporadically, that exhibit mutations producing a progressive neurodegenerative phenotype similar to that observed in human NCL. The study of these mouse models of NCL has dramatically advanced our knowledge of NCL pathophysiology and in some cases has helped delineate the function of proteins mutated in human NCL. In addition, NCL mutant mice have been tested for several different therapeutic approaches and as such they have become important pre-clinical models for validating treatment options. In this review we will assess the current state of mouse models of NCL with regards to their unique pathophysiology and how these mice have helped investigators achieve a better understanding of human NCL disease and therapy.
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PMID:Mouse models of neuronal ceroid lipofuscinoses: useful pre-clinical tools to delineate disease pathophysiology and validate therapeutics. 2250 4