Review
Neurosciences
Bo P. Lear, Darcie L. Moore
Summary: Axon regeneration is limited in the adult mammalian central nervous system due to intrinsic and extrinsic factors. The developmental age can influence the axon growth ability, with embryonic rodents showing longer axons compared to postnatal and adult neurons. This review discusses the advantages and disadvantages of human neuronal model systems and highlights the importance of studying axon growth in human neurons to uncover novel drivers of axon growth in the field of CNS regeneration.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Medicine, Research & Experimental
Yujie Liang, Li Duan, Jianping Lu, Jiang Xia
Summary: Exosomes can be engineered through genetic and chemical methods for targeted drug delivery, increasing the local concentration of therapeutics and minimizing side effects.
Article
Neurosciences
Menghon Cheah, Yuyan Cheng, Veselina Petrova, Anda Cimpean, Pavla Jendelova, Vivek Swarup, Clifford J. Woolf, Daniel H. Geschwind, James W. Fawcett
Summary: Sensory dorsal root ganglion (DRG) neurons in the peripheral branch regenerate readily after injury, but not in the central branch. However, expression of a9 integrin and its activator kindlin-1 (a9k1) enables axons to interact with tenascin-C, promoting extensive regeneration and reconnection of sensory axons in the spinal cord. Transcriptomic analyses of adult male rat DRG neurons revealed that a9k1 expression upregulates a known peripheral nerve regeneration program. Coupling a9k1 treatment with dorsal root axotomy leads to extensive central axonal regeneration, accompanied by the expression of a distinctive CNS regeneration program involving genes associated with ubiquitination, autophagy, ER, trafficking, and signaling. Pharmacological inhibition of these processes blocks axon regeneration, validating their causal contributions to sensory regeneration.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Anastasiya V. Kosykh, Maria B. Tereshina, Nadya G. Gurskaya
Summary: The review investigates the role of molecular players, specifically the AGR family proteins, in scarless wound healing (WH) and their unique potential in enhancing WH processes in postnatal mammals. AGR2 is expressed during scarless WH in embryonic skin, while in adults, its activity is normally inhibited and is observed only in the mucous epithelium of the digestive tract capable of full regeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Veselina Petrova, Bart Nieuwenhuis, James W. Fawcett, Richard Eva
Summary: The research focuses on utilizing various axonal organelles to promote regeneration in the injured adult CNS, highlighting their importance in developmental axon growth and discussing how they can be targeted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Zheng Ying, Na Ye, Qilian Ma, Fan Chen, Ningning Li, Xuechu Zhen
Summary: Significant evidences show that sub-cellular organelle dynamics play a critical role in physiological and pathological events, making them attractive drug targets. However, drug development in this field is still limited despite extensive studies on the biological mechanisms. This review explores the potential of targeting organelle dynamics in the central nervous system, specifically mitochondrial dynamics and ER-organelle membrane contact dynamics, for treating neurodegenerative diseases.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Axel H. Meyer, Thomas M. Feldsien, Mario Mezler, Christopher Untucht, Ramakrishna Venugopalan, Didier R. Lefebvre
Summary: The blood-brain barrier poses a significant challenge for the development of systemically delivered drugs for CNS diseases, resulting in a large unmet need for treatment. Novel therapeutic entities, such as gene therapy and degradomers, have gained popularity but have not been focused on CNS indications. To fully utilize their potential, innovative delivery technologies are likely required for successful drug development. In this article, we discuss and evaluate invasive and non-invasive approaches that can enable or enhance the development of these novel therapeutics for CNS diseases.
Article
Pharmacology & Pharmacy
Yanwen Zheng, Fanhua Kong, Songyang Liu, Xi Liu, Dongni Pei, Xiongying Miao
Summary: Triptolide is a diterpenoid triepoxide with broad antitumor efficacy, but limited by lack of mechanism of action, toxicity, and poor solubility. This study successfully enhanced its anticancer efficacy against hepatocellular carcinoma and mitigated toxicity through drug delivery system design and molecular mechanism exploration.
Article
Biology
Eugene A. Katrukha, Daphne Jurriens, Desiree M. Salas Pastene, Lukas C. Kapitein
Summary: The study reveals the nanoscale organization of neuronal microtubule network in rat hippocampal neurons, showing enrichment of acetylated microtubules in the core of dendrites and tyrosinated microtubules near the plasma membrane. The absolute number of acetylated and tyrosinated microtubules within dendrites was quantified, providing insights into the spatial regulation of intracellular transport facilitated by different motor proteins.
Article
Engineering, Biomedical
Long Chen, Xiongbo Song, Zhicheng Yao, Conglai Zhou, Junjun Yang, Qiming Yang, Junrong Chen, Jiarui Wu, Zeyu Sun, Liling Gu, Yi Ma, Shin-Jae Lee, Chi Zhang, Hai-Quan Mao, Li Sun
Summary: An engineered composite membrane, Gel nanofiber-dAM, consisting of gelatin nanofiber membrane and decellularized amniotic membrane, showed improved mechanical properties and biocompatibility, promoting axon regeneration and reducing fibrotic response in peripheral nerve injury repair. It exhibits great potential for clinical translation in surgical treatment of PNI as a fully natural materials-derived off-the-shelf matrix.
Article
Chemistry, Multidisciplinary
Yuqi Wu, Bingqian Lin, Yinzhu Lu, Liang Li, Kunyue Deng, Suhui Zhang, Huiming Zhang, Chaoyong Yang, Zhi Zhu
Summary: Recently, lysosome targeting chimeras (LYTACs) have been developed to degrade extracellular and membrane proteins through a lysosomal degradation pathway. To overcome the challenges of complex and time-consuming preparation of chimeras, the first aptamer-based LYTAC (Apt-LYTAC) was developed by conjugating aptamers to tri-GalNAc. The Apt-LYTACs efficiently and quickly degrade the extracellular protein PDGF and the membrane protein PTK7, expanding the usage of aptamers and providing a new dimension for targeted protein degradation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Na-Hyun Lee, Sumin You, Ali Taghizadeh, Mohsen Taghizadeh, Hye Sung Kim
Summary: The cell membrane cloaking technique, which utilizes natural design cues, is a promising bioinspired nanotechnology for surface modification of nanoparticles. This technique can replicate complex physicochemical properties and biomimetic functions, thereby enhancing nanotherapeutic platforms. However, there are challenges to be addressed for clinical translation and further research is needed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Matin Hemati-Gourabi, Tuoxin Cao, Megan K. K. Romprey, Meifan Chen
Summary: This review summarizes the positive role of astrocytes in promoting axon regeneration and sprouting in the mature mammalian CNS, along with potential underlying mechanisms. The capacity of astrocytes to support axon growth is context-dependent and influenced by factors such as the local injury environment, neuron-intrinsic regenerative potential, and astrocytes' reactive states.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Engineering, Biomedical
Kelsey G. DeFrates, Daniela Franco, Ellen Heber-Katz, Phillip B. Messersmith
Summary: Traditional approaches in regenerative medicine face limitations in translation and commercialization, prompting the development of therapies that stimulate endogenous processes for regeneration. Recent studies highlight the potential of oxygen-sensing pathways, with upregulation of HIF-1α showing promise in modulating cell metabolism and plasticity for tissue regeneration.
Article
Neurosciences
Xiaoxiao Han, Jiacheng Xu, Zixin Chen, Ping Li, Lili Zhao, Jincheng Tao, Yu Shen, Shengze Zhu, Bin Yu, Jianwei Zhu, Qianqian Cao, Songlin Zhou
Summary: This study reveals that long-noncoding RNA (lncRNA) Gas5 acts as a suppressor for axon regeneration by interacting with soluble Vimentin. The research also demonstrates the regulatory role of Gas5 in both central and peripheral nervous systems, suggesting its potential as a therapeutic target for axon regeneration.
EXPERIMENTAL NEUROLOGY
(2022)