The spinal cord injury (SCI) is a medical and life-disrupting condition with devastating consequences for the physical, social, and professional welfare of patients, and there is no adequate treatment for it. At the same time, gene therapy has been studied as a promising approach for the treatment of neurological and neurodegenerative disorders by delivering remedial genes to the central nervous system (CNS), of which the spinal cord is a part. For gene therapy, multiple vectors have been introduced, including integrating lentiviral vectors and non-integrating adeno-associated virus (AAV) vectors. AAV vectors are a promising system for transgene delivery into the CNS due to their safety profile as well as long-term gene expression. Gene therapy mediated by AAV vectors shows potential for treating SCI by delivering certain genetic information to specific cell types. This review has focused on a potential treatment of SCI by gene therapy using AAV vectors.

• Klíčová slova
• AAV vector, adeno-associated virus, gene therapy, spinal cord injury,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth.

• Klíčová slova
• axon growth, axon regeneration, inter-organelle membrane contact sites, organelles,
• MeSH
• lidé MeSH
• organely metabolismus   patologie   MeSH
• poranění míchy * metabolismus   patologie   terapie   MeSH
• regenerace nervu * MeSH
• růstové kužele metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin's endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system.

• MeSH
• axony metabolismus   fyziologie   MeSH
• centrální nervový systém fyziologie   MeSH
• endoplazmatické retikulum genetika   metabolismus   MeSH
• endozomy metabolismus   MeSH
• fosforylace MeSH
• integriny metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• mutace MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neurony metabolismus   fyziologie   MeSH
• neuroprotektivní látky aplikace a dávkování   MeSH
• poranění nervus opticus farmakoterapie   metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• proteinové domény MeSH
• regenerace nervu * účinky léků   MeSH
• retina účinky léků   fyziologie   MeSH
• vezikulární transportní proteiny aplikace a dávkování   chemie   genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• integriny MeSH
• neuroprotektivní látky MeSH
• vezikulární transportní proteiny MeSH
• ZFYVE27 protein, human MeSH Prohlížeč