Drug delivery to peroxisomes: Employing unique trafficking mechanisms to target protein therapeutics
Peroxisomes are multifunctional organelles of all human cells, responsible for a variety of essential biochemical and metabolic processes including α- and β-oxidation of specific fatty acids, plasmalogen biosynthesis and glyoxylate detoxification. Inborn errors of biogenesis or in the ability to syn...
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| Veröffentlicht in: | Advanced drug delivery reviews 2007-08, Vol.59 (8), p.739-747 |
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| creator | Terlecky, Stanley R. Koepke, Jay I. |
| description | Peroxisomes are multifunctional organelles of all human cells, responsible for a variety of essential biochemical and metabolic processes including α- and β-oxidation of specific fatty acids, plasmalogen biosynthesis and glyoxylate detoxification. Inborn errors of biogenesis or in the ability to synthesize or properly traffic specific enzymes to peroxisomes result in devastating human disease. The organelle has also emerged as a contributor to cellular oxidative stress through its ability to generate hydrogen peroxide. Unlike most other organelles, the peroxisome's import apparatus will accommodate fully folded, oligomeric and co-factor-bound substrates. The strategies outlined here are designed to take advantage of this unique mechanism to target protein therapeutics. Emphasis is also placed on how to deliver these bioactive molecules into cells to engage the peroxisomal protein import machine. The critical antioxidant enzyme catalase has been successfully delivered and targeted by many of the approaches detailed herein; these examples will be discussed. |
| doi_str_mv | 10.1016/j.addr.2007.06.005 |
| format | Article |
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Inborn errors of biogenesis or in the ability to synthesize or properly traffic specific enzymes to peroxisomes result in devastating human disease. The organelle has also emerged as a contributor to cellular oxidative stress through its ability to generate hydrogen peroxide. Unlike most other organelles, the peroxisome's import apparatus will accommodate fully folded, oligomeric and co-factor-bound substrates. The strategies outlined here are designed to take advantage of this unique mechanism to target protein therapeutics. Emphasis is also placed on how to deliver these bioactive molecules into cells to engage the peroxisomal protein import machine. 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Inborn errors of biogenesis or in the ability to synthesize or properly traffic specific enzymes to peroxisomes result in devastating human disease. The organelle has also emerged as a contributor to cellular oxidative stress through its ability to generate hydrogen peroxide. Unlike most other organelles, the peroxisome's import apparatus will accommodate fully folded, oligomeric and co-factor-bound substrates. The strategies outlined here are designed to take advantage of this unique mechanism to target protein therapeutics. Emphasis is also placed on how to deliver these bioactive molecules into cells to engage the peroxisomal protein import machine. The critical antioxidant enzyme catalase has been successfully delivered and targeted by many of the approaches detailed herein; these examples will be discussed.</description><subject>Acatalasia - drug therapy</subject><subject>Acatalasia - metabolism</subject><subject>Aging</subject><subject>Biogenesis</subject><subject>Biological Transport, Active</subject><subject>Catalase - metabolism</subject><subject>Drug Delivery Systems</subject><subject>Endosomes - metabolism</subject><subject>Human peroxisomal disorders</subject><subject>Humans</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Hyperoxaluria - drug therapy</subject><subject>Hyperoxaluria - metabolism</subject><subject>Intracellular Space - metabolism</subject><subject>Membrane Proteins - metabolism</subject><subject>Microscopy, Fluorescence</subject><subject>Oxidation-Reduction</subject><subject>Oxidative Stress</subject><subject>Peptides - metabolism</subject><subject>Peroxisomal Disorders - drug therapy</subject><subject>Peroxisomal Disorders - metabolism</subject><subject>Peroxisome-Targeting Signal 1 Receptor</subject><subject>Peroxisomes - drug effects</subject><subject>Peroxisomes - metabolism</subject><subject>Protein transduction</subject><subject>Protein Transport</subject><subject>Reactive oxygen species</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Targeting signals</subject><subject>Zellweger Syndrome - drug therapy</subject><subject>Zellweger Syndrome - metabolism</subject><issn>0169-409X</issn><issn>1872-8294</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhD3BAOXFLGDvxF-KCSmmRKnEBiZvl2JOtl3xhO1X335NoV-JGTyONnvfVaB5C3lKoKFDx4VBZ72PFAGQFogLgz8iOKslKxXTznOxWSJcN6F8X5FVKBwDKpICX5IJKwbUCsSP-S1z2hcc-PGA8FnkqZozTY0jTgOljcT3M_XQM475YxvBnwSJH23XB_d5WA7p7O4Y0pC2XbdxjLuY4ZQxjke8x2hmXHFx6TV50tk_45jwvyc-v1z-ubsu77zffrj7fla6hIpeaNYI2tfa-RipBd52oLYeWtcrXUmINKEEpp1rQyIVVnLeybZhF2grb8fqSvD_1rkesx6ZshpAc9r0dcVqSEYoxwQU8CdZMAdeNehKkWikq6AayE-jilFLEzswxDDYeDQWz2TIHs9kymy0Dwqy21tC7c_vSDuj_Rc56VuDTCcD1aw8Bo0ku4OjQh4guGz-F__X_BY-Ap3A</recordid><startdate>20070810</startdate><enddate>20070810</enddate><creator>Terlecky, Stanley R.</creator><creator>Koepke, Jay I.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7U5</scope><scope>L7M</scope><scope>7X8</scope></search><sort><creationdate>20070810</creationdate><title>Drug delivery to peroxisomes: Employing unique trafficking mechanisms to target protein therapeutics</title><author>Terlecky, Stanley R. ; Koepke, Jay I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-92461439dd3e1709ff63a50b2b8d377e30e7088c8b09e56a855b7b42ae1b6af53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acatalasia - drug therapy</topic><topic>Acatalasia - metabolism</topic><topic>Aging</topic><topic>Biogenesis</topic><topic>Biological Transport, Active</topic><topic>Catalase - metabolism</topic><topic>Drug Delivery Systems</topic><topic>Endosomes - metabolism</topic><topic>Human peroxisomal disorders</topic><topic>Humans</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Hyperoxaluria - drug therapy</topic><topic>Hyperoxaluria - metabolism</topic><topic>Intracellular Space - metabolism</topic><topic>Membrane Proteins - metabolism</topic><topic>Microscopy, Fluorescence</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Stress</topic><topic>Peptides - metabolism</topic><topic>Peroxisomal Disorders - drug therapy</topic><topic>Peroxisomal Disorders - metabolism</topic><topic>Peroxisome-Targeting Signal 1 Receptor</topic><topic>Peroxisomes - drug effects</topic><topic>Peroxisomes - metabolism</topic><topic>Protein transduction</topic><topic>Protein Transport</topic><topic>Reactive oxygen species</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Targeting signals</topic><topic>Zellweger Syndrome - drug therapy</topic><topic>Zellweger Syndrome - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Terlecky, Stanley R.</creatorcontrib><creatorcontrib>Koepke, Jay I.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Advanced drug delivery reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Terlecky, Stanley R.</au><au>Koepke, Jay I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Drug delivery to peroxisomes: Employing unique trafficking mechanisms to target protein therapeutics</atitle><jtitle>Advanced drug delivery reviews</jtitle><addtitle>Adv Drug Deliv Rev</addtitle><date>2007-08-10</date><risdate>2007</risdate><volume>59</volume><issue>8</issue><spage>739</spage><epage>747</epage><pages>739-747</pages><issn>0169-409X</issn><eissn>1872-8294</eissn><abstract>Peroxisomes are multifunctional organelles of all human cells, responsible for a variety of essential biochemical and metabolic processes including α- and β-oxidation of specific fatty acids, plasmalogen biosynthesis and glyoxylate detoxification. Inborn errors of biogenesis or in the ability to synthesize or properly traffic specific enzymes to peroxisomes result in devastating human disease. The organelle has also emerged as a contributor to cellular oxidative stress through its ability to generate hydrogen peroxide. Unlike most other organelles, the peroxisome's import apparatus will accommodate fully folded, oligomeric and co-factor-bound substrates. The strategies outlined here are designed to take advantage of this unique mechanism to target protein therapeutics. Emphasis is also placed on how to deliver these bioactive molecules into cells to engage the peroxisomal protein import machine. The critical antioxidant enzyme catalase has been successfully delivered and targeted by many of the approaches detailed herein; these examples will be discussed.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>17659806</pmid><doi>10.1016/j.addr.2007.06.005</doi><tpages>9</tpages></addata></record> |
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| subjects | Acatalasia - drug therapy Acatalasia - metabolism Aging Biogenesis Biological Transport, Active Catalase - metabolism Drug Delivery Systems Endosomes - metabolism Human peroxisomal disorders Humans Hydrogen Peroxide - metabolism Hyperoxaluria - drug therapy Hyperoxaluria - metabolism Intracellular Space - metabolism Membrane Proteins - metabolism Microscopy, Fluorescence Oxidation-Reduction Oxidative Stress Peptides - metabolism Peroxisomal Disorders - drug therapy Peroxisomal Disorders - metabolism Peroxisome-Targeting Signal 1 Receptor Peroxisomes - drug effects Peroxisomes - metabolism Protein transduction Protein Transport Reactive oxygen species Receptors, Cytoplasmic and Nuclear - metabolism Targeting signals Zellweger Syndrome - drug therapy Zellweger Syndrome - metabolism |
| title | Drug delivery to peroxisomes: Employing unique trafficking mechanisms to target protein therapeutics |
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