PMID- 35259823
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1673-5374 (Print)
IS  - 1876-7958 (Electronic)
IS  - 1673-5374 (Linking)
VI  - 17
IP  - 10
DP  - 2022 Oct
TI  - Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for 
      axon regeneration after central nervous system injury.
PG  - 2157-2165
LID - 10.4103/1673-5374.335830 [doi]
AB  - Injuries to the central nervous system (CNS) such as stroke, brain, and spinal 
      cord trauma often result in permanent disabilities because adult CNS neurons only 
      exhibit limited axon regeneration. The brain has a surprising intrinsic 
      capability of recovering itself after injury. However, the hostile extrinsic 
      microenvironment significantly hinders axon regeneration. Recent advances have 
      indicated that the inactivation of intrinsic regenerative pathways plays a 
      pivotal role in the failure of most adult CNS neuronal regeneration. 
      Particularly, substantial evidence has convincingly demonstrated that the 
      mechanistic target of rapamycin (mTOR) signaling is one of the most crucial 
      intrinsic regenerative pathways that drive axonal regeneration and sprouting in 
      various CNS injuries. In this review, we will discuss the recent findings and 
      highlight the critical roles of mTOR pathway in axon regeneration in different 
      types of CNS injury. Importantly, we will demonstrate that the reactivation of 
      this regenerative pathway can be achieved by blocking the key mTOR signaling 
      components such as phosphatase and tensin homolog (PTEN). Given that multiple 
      mTOR signaling components are endogenous inhibitory factors of this pathway, we 
      will discuss the promising potential of RNA-based therapeutics which are 
      particularly suitable for this purpose, and the fact that they have attracted 
      substantial attention recently after the success of coronavirus disease 2019 
      vaccination. To specifically tackle the blood-brain barrier issue, we will review 
      the current technology to deliver these RNA therapeutics into the brain with a 
      focus on nanoparticle technology. We will propose the clinical application of 
      these RNA-mediated therapies in combination with the brain-targeted drug delivery 
      approach against mTOR signaling components as an effective and feasible 
      therapeutic strategy aiming to enhance axonal regeneration for functional 
      recovery after CNS injury.
FAU - Li, Ming-Xi
AU  - Li MX
AD  - Clinical Neuroscience Institute, The First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong Province, China.
FAU - Weng, Jing-Wen
AU  - Weng JW
AD  - Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, 
      University of Hong Kong, Hong Kong Special Administrative Region, China.
FAU - Ho, Eric S
AU  - Ho ES
AD  - Department of Biology and Department of Computer Science, Lafayette College, 
      Easton, PA, USA.
FAU - Chow, Shing Fung
AU  - Chow SF
AD  - Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, 
      University of Hong Kong, Hong Kong Special Administrative Region, China.
FAU - Tsang, Chi Kwan
AU  - Tsang CK
AD  - Clinical Neuroscience Institute, The First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong Province, China.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - India
TA  - Neural Regen Res
JT  - Neural regeneration research
JID - 101316351
PMC - PMC9083176
OTO - NOTNLM
OT  - CNS injury
OT  - PTEN
OT  - RNA-based therapeutics
OT  - axon regeneration
OT  - axon sprouting
OT  - brain targeted drug delivery
OT  - ischemic stroke
OT  - mTOR
OT  - nanoparticle
OT  - neural circuit reconstruction
COIS- None
EDAT- 2022/03/10 06:00
MHDA- 2022/03/10 06:01
PMCR- 2022/02/28
CRDT- 2022/03/09 01:45
PHST- 2022/03/09 01:45 [entrez]
PHST- 2022/03/10 06:00 [pubmed]
PHST- 2022/03/10 06:01 [medline]
PHST- 2022/02/28 00:00 [pmc-release]
AID - NeuralRegenRes_2022_17_10_2157_335830 [pii]
AID - NRR-17-2157 [pii]
AID - 10.4103/1673-5374.335830 [doi]
PST - ppublish
SO  - Neural Regen Res. 2022 Oct;17(10):2157-2165. doi: 10.4103/1673-5374.335830.