5 results on '"Ahmed, Zubair"'
Search Results
2. Overexpression of Reticulon 3 Enhances CNS Axon Regeneration and Functional Recovery after Traumatic Injury.
- Author
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Alhajlah S, Thompson AM, and Ahmed Z
- Subjects
- Animals, Axons pathology, Behavior, Animal, Carrier Proteins genetics, Cells, Cultured, Disease Models, Animal, Female, Ganglia, Spinal pathology, Motor Activity, Optic Nerve Injuries genetics, Optic Nerve Injuries pathology, Optic Nerve Injuries physiopathology, Rats, Sprague-Dawley, Retinal Ganglion Cells pathology, Signal Transduction, Spinal Cord Injuries genetics, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology, Up-Regulation, Vesicular Transport Proteins genetics, Vesicular Transport Proteins metabolism, Rats, Axons metabolism, Carrier Proteins metabolism, Ganglia, Spinal metabolism, Nerve Regeneration, Neuronal Outgrowth, Optic Nerve Injuries metabolism, Retinal Ganglion Cells metabolism, Spinal Cord Injuries metabolism
- Abstract
CNS neurons are generally incapable of regenerating their axons after injury due to several intrinsic and extrinsic factors, including the presence of axon growth inhibitory molecules. One such potent inhibitor of CNS axon regeneration is Reticulon (RTN) 4 or Nogo-A. Here, we focused on RTN3 as its contribution to CNS axon regeneration is currently unknown. We found that RTN3 expression correlated with an axon regenerative phenotype in dorsal root ganglion neurons (DRGN) after injury to the dorsal columns, a well-characterised model of spinal cord injury. Overexpression of RTN3 promoted disinhibited DRGN neurite outgrowth in vitro and dorsal column axon regeneration/sprouting and electrophysiological, sensory and locomotor functional recovery after injury in vivo. Knockdown of protrudin, however, ablated RTN3-enhanced neurite outgrowth/axon regeneration in vitro and in vivo. Moreover, overexpression of RTN3 in a second model of CNS injury, the optic nerve crush injury model, enhanced retinal ganglion cell (RGC) survival, disinhibited neurite outgrowth in vitro and survival and axon regeneration in vivo, an effect that was also dependent on protrudin. These results demonstrate that RTN3 enhances neurite outgrowth/axon regeneration in a protrudin-dependent manner after both spinal cord and optic nerve injury.
- Published
- 2021
- Full Text
- View/download PDF
3. Pigment Epithelium-Derived Factor Promotes Axon Regeneration and Functional Recovery After Spinal Cord Injury.
- Author
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Stevens AR, Ahmed U, Vigneswara V, and Ahmed Z
- Subjects
- Animals, Axons drug effects, Cell Survival drug effects, Disease Models, Animal, Female, Ganglia, Spinal drug effects, Ganglia, Spinal metabolism, Nerve Growth Factors metabolism, Neurites drug effects, Neurites metabolism, Neuroprotection drug effects, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Sprague-Dawley, Receptors, Nerve Growth Factor metabolism, Sciatic Nerve drug effects, Sciatic Nerve physiopathology, Signal Transduction drug effects, Spinal Cord Injuries pathology, Up-Regulation drug effects, Axons physiology, Eye Proteins pharmacology, Nerve Growth Factors pharmacology, Nerve Regeneration drug effects, Recovery of Function drug effects, Serpins pharmacology, Spinal Cord Injuries physiopathology
- Abstract
Although neurons in the adult mammalian CNS are inherently incapable of regeneration after injury, we previously showed that exogenous delivery of pigment epithelium-derived factor (PEDF), a 50-kDa neurotrophic factor (NTF), promoted adult retinal ganglion cell neuroprotection and axon regeneration. Here, we show that PEDF and other elements of the PEDF pathway are highly upregulated in dorsal root ganglion neurons (DRGN) from regenerating dorsal column (DC) injury paradigms when compared with non-regenerating DC injury models. Exogenous PEDF was neuroprotective to adult DRGN and disinhibited neurite outgrowth, whilst overexpression of PEDF after DC injury in vivo promoted significant DC axon regeneration with enhanced electrophysiological, sensory, and locomotor function. Our findings reveal that PEDF is a novel NTF for adult DRGN and may represent a therapeutically useful factor to promote functional recovery after spinal cord injury.
- Published
- 2019
- Full Text
- View/download PDF
4. BMP4/Smad1 Signalling Promotes Spinal Dorsal Column Axon Regeneration and Functional Recovery After Injury.
- Author
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Farrukh F, Davies E, Berry M, Logan A, and Ahmed Z
- Subjects
- Animals, Carrier Proteins metabolism, Dependovirus metabolism, Female, Ganglia, Spinal metabolism, Neuronal Outgrowth, Rats, Sprague-Dawley, TOR Serine-Threonine Kinases metabolism, Axons physiology, Bone Morphogenetic Protein 4 metabolism, Nerve Regeneration physiology, Recovery of Function, Signal Transduction, Smad1 Protein metabolism, Spinal Cord Injuries metabolism, Spinal Cord Injuries physiopathology
- Abstract
Signalling through the BMP4/Smad1 pathway promotes corticospinal tract axon regeneration and functional recovery in mice. However, unlike humans and rats, mice do not cavitate. Here, we investigated if activation of the BMP4/Smad1 pathway promotes axon regeneration and functional recovery in a rat model that cavitates. We show that dorsal root ganglion neurons (DRGN) in injury models, including the non-regenerating dorsal column (DC) and the regenerating sciatic nerve (SN) crush and preconditioning (p) SN + DC (pSN + DC) paradigms, regulate the BMP4/Smad1 signalling pathway. For example, mRNA expression of positive regulators of the BMP4/Smad1 pathway was highly up-regulated whilst negative regulators were significantly down-regulated in DRGN in the regenerating SN and pSN + DC models compared to non-regenerating DC models, matched by concomitant changes in protein expression detected in DRGN by immunohistochemistry. BMP4 peptide promoted significant DRGN survival and disinhibited neurite outgrowth in vitro, whilst AAV-BMP4 delivery in vivo stimulated DC axon regeneration and functional recovery in a model that cavitates. Our results show that activation of the BMP4/Smad1 pathway is a potential therapeutic target in the search for axon regenerative signalling pathways in the CNS.
- Published
- 2019
- Full Text
- View/download PDF
5. Prospects for mTOR-mediated functional repair after central nervous system trauma.
- Author
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Berry, Martin, Ahmed, Zubair, Morgan-Warren, Peter, Fulton, Daniel, and Logan, Ann
- Subjects
- *
MTOR protein , *DEVELOPMENTAL neurobiology , *CELLULAR signal transduction , *PROTEIN kinase B , *AXONS , *NERVOUS system regeneration , *SPINAL cord injuries - Abstract
Recent research has suggested that the growth of central nervous system (CNS) axons during development is mediated through the PI3K/Akt/mammalian target of rapamycin (mTOR) intracellular signalling axis and that suppression of activity in this pathway occurs during maturity as levels of the phosphatase and tensin homologue (PTEN) rise and inhibit PI3K activation of mTOR, accounting for the failure of axon regeneration in the injured adult CNS. This hypothesis is supported by findings confirming that suppression of PTEN in experimental adult animals promotes impressive axon regeneration in the injured visual and corticospinal motor systems. This review focuses on these recent developments, discussing the therapeutic potential of a mTOR-based treatment aimed at promoting functional recovery in CNS trauma patients, recognising that to fulfil this ambition, the new therapy should aim to promote not only axon regeneration but also remyelination of regenerated axons, neuronal survival and re-innervation of denervated targets through accurate axonal guidance and synaptogenesis, all with minimal adverse effects. The translational challenges presented by the implementation of this new axogenic therapy are also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
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