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<p>Glial-derived neurotrophic factor (GDNF) is under active study as a therapeutic agent for the treatment of age-related neurodegenerative diseases and traumatic neuron death. Interest in further fundamental research on this factor arises from excellent results from preclinical studies and the failures of phase II clinical trials of GDNF in Parkinson’s disease. Several hypotheses have been put forward to explain this: problems associated with the delivery of high-molecular weight drugs, the high affinity of GDNF for heparin and heparin- like molecules, which prevents biodistribution in the cerebral parenchyma, the structure of the protein used, which differs from the native form, and the presence of different isoforms of the protein. All these issues clearly require additional research on GDNF at the gene, RNA, and protein levels. This review is an attempt to focus on the latest data on GDNF, developments aimed at solving the problems encountered, and the probabilities of its therapeutic application in human neurodegenerative diseases.</p>

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Fundamental Research On and Practical Application Of GDNF as a Neuroprotective Agent in Neurodegenerative Diseases

  • 期刊论文

  • 发表日期：

    2025年3月1日

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  • D. V. Shamadykova,
  • G. V. Pavlova

摘要

Glial-derived neurotrophic factor (GDNF) is under active study as a therapeutic agent for the treatment of age-related neurodegenerative diseases and traumatic neuron death. Interest in further fundamental research on this factor arises from excellent results from preclinical studies and the failures of phase II clinical trials of GDNF in Parkinson’s disease. Several hypotheses have been put forward to explain this: problems associated with the delivery of high-molecular weight drugs, the high affinity of GDNF for heparin and heparin- like molecules, which prevents biodistribution in the cerebral parenchyma, the structure of the protein used, which differs from the native form, and the presence of different isoforms of the protein. All these issues clearly require additional research on GDNF at the gene, RNA, and protein levels. This review is an attempt to focus on the latest data on GDNF, developments aimed at solving the problems encountered, and the probabilities of its therapeutic application in human neurodegenerative diseases.