Growth differentiation factor 5: a neurotrophic factor with neuroprotective potential in Parkinson's disease
Susan R.Goulding1
Jayanth Anantha1
Louise M.Collins2
Aideen M.Sullivan1
Gerard W.O'Keeffe1
1.Department of Anatomy and Neuroscience,and Cork Neuroscience Centre,University College Cork,Cork,Ireland2.Department of Anatomy and Neuroscience,and Cork Neuroscience Centre,University College Cork,Cork,Ireland;Department of Physiology,University College Cork,Cork,Ireland
摘要：Parkinson's disease is the most common movement disorder worldwide, affecting over 6 million people. It is an age-related disease, occurring in 1％ of people over the age of 60, and 3％ of the population over 80 years. The disease is characterized by the progressive loss of midbrain dopaminergic neurons from the substantia nigra, and their axons, which innervate the striatum, resulting in the characteristic motor and non-motor symptoms of Parkinson's disease. This is paralleled by the intracellular accumulation of α-synuclein in several regions of the nervous system. Current therapies are solely symptomatic and do not stop or slow disease progression. One promising disease-modifying strategy to arrest the loss of dopaminergic neurons is the targeted delivery of neurotrophic factors to the substantia nigra or striatum, to protect the remaining dopaminergic neurons of the nigrostriatal pathway. However, clinical trials of two well-established neurotrophic factors, glial cell line-derived neurotrophic factor and neurturin, have failed to meet their primary end-points. This failure is thought to be at least partly due to the downregulation by α-synuclein of Ret, the common co-receptor of glial cell line-derived neurorophic factor and neurturin. Growth/differentiation factor 5 is a member of the bone morphogenetic protein family of neurotrophic factors, that signals through the Ret-independent canonical Smad signaling pathway. Here, we review the evidence for the neurotrophic potential of growth/differentiation factor 5 in in vitro and in vivo models of Parkinson's disease. We discuss new work on growth/differentiation factor 5's mechanisms of action, as well as data showing that viral delivery of growth/differentiation factor 5 to the substantia nigra is neuroprotective in the α-synuclein rat model of Parkinson's disease. These data highlight the potential for growth/differentiation factor 5 as a disease-modifying therapy for Parkinson's disease.
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论文发表日期：2022-01-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 38-44 )
英文信息