Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

Padel, Thomas; Özen, Ilknur; Boix, Jordi; Barbariga, Marco; Gaceb, Abderahim; Roth, Michaela; Paul, Gesine

doi:10.1016/j.nbd.2016.06.002

Cited by 49 publications

(42 citation statements)

References 47 publications

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“…For example, Albright et al ( 2016 ) found that a population of nestin-positive cells contributes to dopaminergic neuron turnover in this brain structure (Albright et al, 2016 ). Furthermore, using a 6-OHDA mouse model, Padel et al ( 2016 ) also showed that platelet-derived growth factor (PDGF) can lead to the restoration of nigrostriatal fiber tracts (Padel et al, 2016 ).…”

Section: “Novel” Adult Neurogenic Zonesmentioning

confidence: 99%

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Jurkowski

Bettio

Woo

et al. 2020

Front. Cell. Neurosci.

152

109

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Convincing evidence has repeatedly shown that new neurons are produced in the mammalian brain into adulthood. Adult neurogenesis has been best described in the hippocampus and the subventricular zone (SVZ), in which a series of distinct stages of neuronal development has been well characterized. However, more recently, new neurons have also been found in other brain regions of the adult mammalian brain, including the hypothalamus, striatum, substantia nigra, cortex, and amygdala. While some studies have suggested that these new neurons originate from endogenous stem cell pools located within these brain regions, others have shown the migration of neurons from the SVZ to these regions. Notably, it has been shown that the generation of new neurons in these brain regions is impacted by neurologic processes such as stroke/ischemia and neurodegenerative disorders. Furthermore, numerous factors such as neurotrophic support, pharmacologic interventions, environmental exposures, and stem cell therapy can modulate this endogenous process. While the presence and significance of adult neurogenesis in the human brain (and particularly outside of the classical neurogenic regions) is still an area of debate, this intrinsic neurogenic potential and its possible regulation through therapeutic measures present an exciting alternative for the treatment of several neurologic conditions. This review summarizes evidence in support of the classic and novel neurogenic zones present within the mammalian brain and discusses the functional significance of these new neurons as well as the factors that regulate their production. Finally, it also discusses the potential clinical applications of promoting neurogenesis outside of the classical neurogenic niches, particularly in the hypothalamus, cortex, striatum, substantia nigra, and amygdala.

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Section: “Novel” Adult Neurogenic Zonesmentioning

confidence: 99%

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Jurkowski

Bettio

Woo

et al. 2020

Front. Cell. Neurosci.

152

109

View full text Add to dashboard Cite

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“…Intracerebroventricular administration of exogenous PDGF-BB has entered human clinical trials and appears to be well-tolerated and safe [ 115 ]. Thus, in a cell culture model, BBB function is better maintained in hypoxia when PDGF-BB or TGFβ is administered [ 132 ]; in status epilepticus, intravenous administration of PDGF-BB reduces blood vessel leakage and normalises blood flow [ 4 ]; and in an animal model of Parkinson’s disease, PDGF-BB may restore neurovascular function by rescuing PDGFRβ signalling [ 111 ].…”

Section: Targeting Pericytes To Ameliorate Brain Disordersmentioning

confidence: 99%

Targeting pericytes for therapeutic approaches to neurological disorders

et al. 2018

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Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood–brain barrier. Pericytes, an under-studied cell type located on capillaries, are of crucial importance in regulating diverse microvascular functions, such as angiogenesis, the blood–brain barrier, capillary blood flow and the movement of immune cells into the brain. They also form part of the “glial” scar isolating damaged parts of the CNS, and may have stem cell-like properties. Recent studies have suggested that pericytes play a crucial role in neurological diseases, and are thus a therapeutic target in disorders as diverse as stroke, traumatic brain injury, migraine, epilepsy, spinal cord injury, diabetes, Huntington’s disease, Alzheimer’s disease, diabetes, multiple sclerosis, glioma, radiation necrosis and amyotrophic lateral sclerosis. Here we report recent advances in our understanding of pericyte biology and discuss how pericytes could be targeted to develop novel therapeutic approaches to neurological disorders, by increasing blood flow, preserving blood–brain barrier function, regulating immune cell entry to the CNS, and modulating formation of blood vessels in, and the glial scar around, damaged regions.

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“…Interestingly, a 6-OHDA lesion in mice has been associated with a pathological activation of pericytes that was normalized upon ICV administration of PDGF-BB and, as previously reported, led to nigrostriatal restoration and behavioral recovery (Padel et al, 2016). PDGF-BB is known to be secreted by endothelial cells and binds the PDGFRβ on pericytes to recruit these cells to the vessel wall and to stabilize blood vessels (Sweeney, Ayyadurai, & Zlokovic, 2016;.…”

Section: Platelet-derived Growth Factormentioning

confidence: 74%

Trophic factors for Parkinson's disease: Where are we and where do we go from here?

Paul

Sullivan

2018

Eur J of Neuroscience

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Perhaps the most important unmet clinical need in Parkinson's disease (PD) is the development of a therapy that can slow or halt disease progression. Extensive preclinical research has provided evidence for the neurorestorative properties of several growth factors, yet only a few have been evaluated in clinical studies. Attempts to achieve neuroprotection by addressing cell-autonomous mechanisms and targeting dopaminergic neurons have been disappointing. Four different trophic factors have so far entered clinical trials in PD: glial cell line-derived growth factor, its close structural and functional analog neurturin, platelet-derived growth factor and cerebral dopaminergic neurotrophic factor. This article reviews the pre-clinical evidence for the neuroprotective and neurorestorative actions of these growth factors and discusses limitations of preclinical models, which may hamper successful translation to the clinic. We summarize the previous and ongoing clinical trials using growth factors in PD and emphasize the caveats in clinical trial design that may prevent the further development and registration of potentially neuroprotective and neurorestorative treatments for individuals suffering from PD.

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Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

Cited by 49 publications

References 47 publications

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Targeting pericytes for therapeutic approaches to neurological disorders

Trophic factors for Parkinson's disease: Where are we and where do we go from here?

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