Pronase is a commercially available mixture of proteinases isolated from the extracellular fluid of Streptomyces griseus. Activity extends to both denatured and native proteins leading to complete or nearly complete digestion into individual amino acids.
Neprilysin is also associated with other biochemical processes, and is particularly highly expressed in kidney and lung tissues. Inhibitors have been designed with the aim of developing analgesic and antihypertensive agents that act by preventing neprilysin’s activity against signaling peptides such as enkephalins, substance P, endothelin, and atrial natriuretic factor.[8][9]
Associations have been observed between neprilysin expression and various types of cancer; however, the relationship between neprilysin expression and carcinogenesis remains obscure. In cancer biomarker studies, the neprilysin gene is often referred to as CD10 or CALLA. In some types of cancer, such as metastatic carcinoma and some advanced melanomas, neprilysin is overexpressed;[10] in other types, most notably lung cancers, neprilysin is downregulated, and thus unable to modulate the pro-growth autocrine signaling of cancer cells via secreted peptides such as mammalian homologs related to bombesin.[11]
Mutations in the neprilysin gene have been associated with familial forms of Alzheimer’s disease,[2] and neprilysin-deficient knockout mice show both Alzheimer’s-like behavioral impairment and amyloid-beta deposition in the brain,[3] providing strong evidence for the protein’s association with the Alzheimer’s disease process. Because neprilysin is thought to be the rate-limiting step in amyloid beta degradation,[4] it has been considered a potential therapeutic target; compounds such as the peptide hormone somatostatin have been identified that increase the enzyme’s activity level.[5] One hypothesis for the strong dependence of Alzheimer’s incidence on age focuses on the declining production of somatostatin the brains of elderly people, which thus depresses the activity of neprilysin and promotes aggregation of unprocessed amyloid beta.[6] Declining neprilysin activity with increasing age may also be explained by oxidative damage, known to be a causative factor in Alzheimer’s disease; higher levels of inappropriately oxidized neprilysin have been found in Alzheimer’s patients compared to cognitively normal elderly people.[7
Neprilysin, also known as neutral endopeptidase (NEP), CD10, and common acute lymphoblastic leukemia antigen (CALLA), is a zinc-dependent metalloprotease enzyme that degrades a number of small secreted peptides, most notably the amyloid beta peptide whose abnormal misfolding and aggregation in neural tissue has been implicated as a cause of Alzheimer’s disease. Synthesized as a membrane-bound protein, the neprilysin ectodomain is released into the extracellular domain after it has been transported from the Golgi apparatus to the cell surface. In neurons, neprilysin is regulated by the protein nicastrin, a component of the gamma secretase complex that performs a necessary step in processing amyloid precursor protein to amyloid beta.[1
Membrane-bound transcription factor peptidase, site 2 also known as Site-2 Protease (S2P) is an enzyme (EC 3.4.24.85) encoded by the MBTPS2 gene which liberates the N-terminal fragment of sterol regulatory element binding protein (SREBP) transcription factors from membranes.[1][2]
Collagenases are enzymes that break the peptide bonds in collagen.
They assist in destroying extracellular structures in pathogenesis of bacteria such as Clostridium. They are an exotoxin (a virulence factor) and help to facilitate the spread of gas gangrene. They normally target the connective tissue in muscle cells and other body organs.[1]
Collagen, a key component of the animal extracellular matrix, is made through cleavage of pro-collagen by collagenase once it has been secreted from the cell. This stops large structures from forming inside the cell itself.
Collagenase production can be induced during an immune response, by cytokines which stimulate cells such as fibroblasts and osteoblasts, and cause indirect tissue damage.[citation needed]
SANTYL Ointment, a Healthpoint, Ltd. product, is the only FDA approved product containing Collagenase as its primary ingredient.
They are categorized under EC number 3.4.24.
Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. Specifically, alpha secretases cleave within the fragment that gives rise to the Alzheimer’s disease-associated peptide amyloid beta when APP is instead processed by beta secretase and gamma secretase. Thus, alpha-secretase cleavage precludes amyloid beta formation and is considered to be part of the non-amyloidogenic pathway in APP processing. Alpha secretases are members of the ADAM (’a disintegrin and metalloprotease domain’) family, which are expressed on the surfaces of cells and anchored in the cell membrane. Several such proteins, notably ADAM10, have been identified as possessing alpha-secretase activity. Upon cleavage by alpha secretases, APP releases its extracellular domain - a fragment known as APPs? - into the extracellular environment in a process known as ectodomain shedding.[1]ADAM10 consists of two protein domains, a disintegrin domain and a prodomain; however, only the prodomain is required for APP processing.[2] Other ADAM proteins, ADAM17 (also called TACE, tumor necrosis factor-? converting enzyme),[3] ADAM9,[4] and ADAM19[5] have also been identified as alpha secretases; extracellular expression of mutant ADAM9 (also known as MDC9 or meltrin gamma) lacking the membrane anchor domain has been suggested as one of many possible means of Alzheimer’s prevention and treatment exploiting the alpha secretase pathway.[6] Two distinct modalities of alpha-secretase activity have been observed in cells; constitutive activity occurs mainly at the cell surface and is independent of regulatory mechanisms inside the cell, while regulated activity occurs mainly in the golgi and is dependent on the activity of protein kinase C. Alpha-secretase activity in the golgi is thought to compete directly with the beta-secretase pathway for APP substrates during membrane protein maturation.[7] Cell-surface cleavage by alpha secretase is very rapid after APP reaches the cell surface.[8]
The activity of alpha secretases has been implicated in the regulation of learning and memory formation. Release of the APPs? ectodomain has neurotrophic effects that counteract apoptotic signaling and promote synapse formation, processes that are upregulated when ADAM10 is overexpressed.[9] Alpha secretase activity has also been observed to be upregulated in response to the signaling peptide PACAP.[10]
Related alpha-secretases, including ADAM10, have also been implicated in similar maturation events for other transmembrane proteins such as MHC class I proteins. Recent evidence suggests that some such proteins are first processed to ectodomains by alpha secretases and subsequently cleaved by another Alzheimer’s-associated protease complex, gamma secretase in its presenilin-complexed form. [11] The Notch pathway bears many similarities to APP processing and is also regulated in part by ADAM10.[12]
ADAMTS5 (aggrecanase) is an enzyme that destroys cartilage in mice. Its discovery may lead to progress in human arthritis research. This enzyme may also be involved in cartilage deterioration in humans. It has been isolated and identified by Australian scientists in Sydney. ADAMTS5 has been indicated as being important in early osteoarthritis.
Ehlers-Danlos syndrome, dermatosparaxis type is caused by mutations in the ADAMTS2 gene. Several mutations in the ADAMTS2 gene have been identified in people with this syndrome. These mutations greatly reduce the production of the enzyme made by the ADAMTS2 gene. Procollagen cannot be processed correctly without this enzyme. As a result, collagen fibrils are not assembled properly; they appear ribbon-like and disorganized under the microscope. Cross-links, or chemical interactions, between collagen fibrils are also affected. These defects weaken connective tissue (the tissue that binds and supports the body’s muscles, ligaments, organs, and skin), which causes the signs and symptoms of the disorder.
ADAMTS2 (ADAM metallopeptidase with thrombospondin type 1 motif, 2) is a gene that produces an enzyme that is responsible for processing several types of procollagen proteins. Procollagens are the precursors of collagens, the proteins that add strength and support to many body tissues. Specifically, this enzyme clips a short chain of amino acids off one end of the procollagen (Amino acids are the building blocks of proteins). This clipping step is necessary for collagen molecules to function normally and assemble into fibrils outside cells.
The ADAMTS2 gene is located on the long (q) arm of chromosome 5 at the end (terminus) of the arm, from base pair 178,473,473 to base pair 178,704,934.