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| 1 | The potential of bone morphogenetic protein 2 as a neurotrophic factor for Parkinson’s disease显示文摘Parkinson’s disease is the second most common neurodegenerative disorder;it affects 1%of the population over the age of 65.The number of people with Parkinson’s disease is set to rapidly increase due to changing demographics and there is an unmet clinical need for disease-modifying therapies.The pathological hallmarks of Parkinson’s disease are the progressive degeneration of dopaminergic neurons in the substantia nigra and their axons which project to the striatum,and the aggregation ofα-synuclein;these result in a range of debilitating motor and non-motor symptoms.The application of neurotrophic factors to protect and potentially regenerate the remaining dopaminergic neurons is a major area of research interest.However,this strategy has had limited success to date.Clinical trials of two well-known neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have reported limited efficacy in Parkinson’s disease patients,despite these factors showing potent neurotrophic actions in animal studies.There is therefore a need to identify other neurotrophic factors that can protect againstα-synuclein-induced degeneration of dopaminergic neurons.The bone morphogenetic protein(BMP)family is the largest subgroup of the transforming growth factor-βsuperfamily of proteins.BMPs are naturally secreted proteins that play crucial roles throughout the developing nervous system.Importantly,many BMPs have been shown to be potent neurotrophic factors for dopaminergic neurons.Here we discuss recent work showing that transcripts for the BMP receptors and BMP2 are co-expressed with several key markers of dopaminergic neurons in the human substantia nigra,and evidence for downregulation of BMP2 expression at distinct stages of Parkinson’s disease.We also discuss studies that explored the effects of BMP2 treatment,in in vitro and in vivo models of Parkinson’s disease.These studies found potent effects of BMP2 on dopaminergic neurites,which is important given that axon degeneration is increasingly recognized as a key early event in Parkinson’s disease.Thus,the aim of this mini-review is to give an overview of the BMP family and the BMP-Smad signalling pathway,in addition to reviewing the available evidence demonstrating the potential of BMP2 for Parkinson’s disease therapy. | Susan R.Goulding Aideen M.Sullivan Gerard W.O’Keeffe Louise M.Collins | 2020 | Neural Regeneration Research2020，15，8： | 7 |
| 2 | Rapid transport of insulin to the brain following intranasal administration in rats显示文摘We previously reported that intranasal insulin protects substantia nigra dopaminergic neurons against6-hydroxydopamine neurotoxicity in rats. This study aimed to assess insulin pharmacokinetics in the rat brain following intranasal application. Recombinant human insulin(rh-Ins) or phosphate buffer solution was administered to both nostrils of rats. Animals were sacrificed at 15 minutes, 1, 2, and 6 hours to determine insulin levels in different brain regions by an ultrasensitive, human-specific enzyme-linked immunosorbent assay kit. For fluorescence tracing study, rats were administered with intranasal florescence-tagged insulin(Alex546-Ins), and brains were fixed at 10 and 30 minutes to prepare sagittal sections.rh-Ins was detected in all brain regions examined except the cerebral cortex. The highest levels were detected in the brainstem, followed by the cerebellum, substantia nigra/ventral tegmental area, olfactory bulb,striatum, hippocampus, and thalamus/hypothalamus. Insulin levels reached a peak at 15 minutes and then declined gradually overtime, but remained significantly higher than baseline levels at 6 hours in most regions.Consistently, widespread Alex546-Ins-binding cells were detected in the brain at 10 and 30 minutes, with the olfactory bulb and brainstem showing the highest while the cerebral cortex showing lowest fluorescence signals. Double-immunostaining showed that Alex546-Ins-bindings were primarily co-localized with neuronal nuclei-positive neurons. In the subtantia nigra, phospho-Akt was found to be activated in a subset of Alex546-Ins and tyrosine hydroxylase double-labeled cells, suggesting activation of the Akt/PI3 K pathway in these dopaminergic neurons. Data from this study suggest that intranasal insulin could effectively reach deep brain structures including the nigrostriatal pathways, where it binds to dopaminergic neurons and activates intracellular cell survival signaling. This study was approved by the Institutional Animal Care Committee at the University of Mississippi Medical Center(protocol 1333 A) on June 29, 2015. | Lir-Wan Fan Kathleen Carter Abhay Bhatt Yi Pang | 2019 | Neural Regeneration Research2019，14，6： | 4 |
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