Neurotrophic factors for the treatment of Parkinson's disease

Sullivan, Aideen M.; Toulouse, André

doi:10.1016/j.cytogfr.2011.05.001

Cited by 58 publications

(43 citation statements)

References 141 publications

(158 reference statements)

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“…There have been no descriptions of Pitx3 expression in the adult human brainstem. In detailed work in mice with some confirmation in primates, Otx2 expression has been found to be restricted to VTA neurons (Simeone, et al, 2011) with animal studies supporting the concept that its expression contributes to the differential vulnerability between the SNC and VTA in PD Reyes et al 4 (Di Salvio, et al, 2010a).For cell phenotype maintenance, trophic factors are also vital, with factors like GDNF which supports all dopamine neurons (Sullivan and Toulouse, 2011) currently undergoing therapeutic trials in PD (Rangasamy, et al, 2010). A trophic factor receptor with restricted expression to the ventral part of the SNC has been identified in adult mice (Osborne, et al, 2005) and may be important for the maintenance of these most vulnerable neurons.…”

Section: ***Figure 1 About Here***mentioning

confidence: 93%

“…On a cell-by-cell basis, Pitx3 immunoreactivity was found in the vast majority of all brainstem dopamine neurons in aged humans, with the intensity of regional mRNA data reflecting the dopamine cell density observed in these regions. Because Pitx3 has been shown to be important for the regulation of the rate-limiting enzyme for dopamine synthesis (Lebel, et al, 2001) and the regulation of neurotrophic factors (including BDNF and GDNF (Yang, et al, 2008) both of which have been trialed as PD therapeutics (Nagahara andTuszynski, 2011,Sullivan andToulouse, 2011)), and of essential microRNAs for neuronal maintenance (Kim, et al, 2007), its continued expression in adult human dopamine neurons is not surprising.…”

Section: On a Cell-by-cell Basis Adult Human Dopamine Neurons Appearmentioning

confidence: 99%

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Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Reyes

Double

et al. 2013

Neurobiology of Aging

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Recent studies suggest a variety of factors characterize substantia nigra neurons vulnerable to Parkinson's disease, including the transcription factors Pitx3 and Otx2 and the trophic factor receptor DCC, but there is limited information on their expression and localisation in adult humans. Pitx3, Otx2 and DCC were immunohistochemically localised in the upper brainstem of adult humans and mice and protein expression assessed using relative intensity measures and online microarray data. Pitx3 was present and highly expressed in most dopamine neurons. Surprisingly, in our elderly subjects no Otx2 immunoreactivity was detected in dopamine neurons, although Otx2 gene expression was found in younger cases. Enhanced DCC gene expression occurred in the substantia nigra, and higher amounts of DCC protein characterised vulnerable ventral nigral dopamine neurons. Our data show that, at the age when Parkinson's disease typically occurs, there are no significant differences in the expression of transcription factors in brainstem dopamine neurons, but those most vulnerable to Parkinson's disease rely more on the trophic factor receptor DCC than other brainstem dopamine neurons.Key words: deleted in colorectal cancer; dopamine neurons; orthodenticle homeobox 2; Pitx3; substantia nigra Abbreviations: DCC= deleted in colorectal cancer; Otx2= orthodenticle homeobox 2; PD= Parkinson's disease; SNC= substantia nigra pars compacta; TH= tyrosine hydroxylase; VTA= ventral tegmental area Reyes et al. 3

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Section: ***Figure 1 About Here***mentioning

confidence: 93%

Section: On a Cell-by-cell Basis Adult Human Dopamine Neurons Appearmentioning

confidence: 99%

Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Reyes

Double

et al. 2013

Neurobiology of Aging

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“…In support of this role, BMPs (including BMP2) and BMPRs have been shown to be expressed in the midbrain and striatum from 6-24 months in the adult rat (Chen et al 2003). Furthermore, in animal models of PD, exogenous GDF5 delivery into the nigrostriatal pathway has potent survival-promoting effects on adult nigral DA neurons (Sullivan et al 1997(Sullivan et al , 1999Hurley et al 2004;O'Sullivan et al 2010;Sullivan and Toulouse 2011). Disruption to the normal expression of BMPRs may thus render nigrostriatal DA neurons more vulnerable to degeneration and increase the risk of the development of PD.…”

Section: Discussionmentioning

confidence: 99%

Canonical BMP–Smad Signalling Promotes Neurite Growth in Rat Midbrain Dopaminergic Neurons

et al. 2014

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Ventral midbrain (VM) dopaminergic (DA) neurons project to the dorsal striatum via the nigrostriatal pathway to regulate voluntary movements, and their loss leads to the motor dysfunction seen in Parkinson's disease (PD). Despite recent progress in the understanding of VM DA neurogenesis, the factors regulating nigrostriatal pathway development remain largely unknown. The bone morphogenetic protein (BMP) family regulates neurite growth in the developing nervous system and may contribute to nigrostriatal pathway development. Two related members of this family, BMP2 and growth differentiation factor (GDF)5, have neurotrophic effects, including promotion of neurite growth, on cultured VM DA neurons. However, the molecular mechanisms regulating their effects on DA neurons are unknown. By characterising the temporal expression profiles of endogenous BMP receptors (BMPRs) in the developing and adult rat VM and striatum, this study identified BMP2 and GDF5 as potential regulators of nigrostriatal pathway development. Furthermore, through the use of noggin, dorsomorphin and BMPR/Smad plasmids, this study demonstrated that GDF5-and BMP2-induced neurite outgrowth from cultured VM DA neurons is dependent on BMP type I receptor activation of the Smad 1/5/8 signalling pathway.

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“…3 Thus, current research efforts are focused on halting neurodegeneration using promising alternatives such as antioxidants, antiapoptotic agents, cell-based therapies, and neuroprotective agents. 4 An interesting and promising approach is the use of growth factors (GFs), and specifically the subfamily of the neurotrophic factors (NTFs), which are potentially enara herrán 1,2 catalina requejo 3 Jose angel ruiz-Ortega …”

Section: Introductionmentioning

confidence: 99%

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease

Herrán¹,

Requejo²,

Ruiz-Ortega³

et al. 2014

IJN

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Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson’s disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson’s disease.

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Neurotrophic factors for the treatment of Parkinson's disease

Cited by 58 publications

References 141 publications

Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Canonical BMP–Smad Signalling Promotes Neurite Growth in Rat Midbrain Dopaminergic Neurons

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease

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Neurotrophic factors for the treatment of Parkinson's disease

Cited by 58 publications

References 141 publications

Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Canonical BMP–Smad Signalling Promotes Neurite Growth in Rat Midbrain Dopaminergic Neurons

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson&rsquo;s disease

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Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease