Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson’s Disease

Garea-Rodríguez, Enrique; Eesmaa, Ave; Lindholm, Päivi; Schlumbohm, Christina; König, Jessica; Meller, B.; Krieglstein, Kerstin; Helms, Gunther; Saarma, Märt; Fuchs, Eberhard

doi:10.1371/journal.pone.0149776

Cited by 46 publications

(39 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although CDNF/MANF proteins can be secreted like other classical NTFs (Oh‐Hashi et al, ; Henderson et al, ; Garea‐Rodriguez et al, ), they also can function in the ER as ER stress response protein (Cheng et al, ; Liu et al, ; Kim et al, ). The protective effect of MANF in ER stress has been demonstrated (Apostolou et al, ; Glembotski et al, ; Zhao et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike all other classical NTFs that are solely secreted proteins, CDNF/MANF present unique protein structure and function (Lindstrom et al, ; Norisada et al, ). They can secrete out the cells like other NTFs, but can also locate in the cells (Voutilainen et al, ; Garea‐Rodriguez et al, ). Thus, Voutilainen et al () proposed the hypothetical dual mode of action about CDNF/MANF.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Quantitative analysis on secretion level of CDNF regulated by two key α‐helices in CDNF protein

Líu

Zhong

Zhao

et al. 2019

Cell Biology International

View full text Add to dashboard Cite

Cerebral dopamine neurotrophic factor (CDNF) has been considered as potent candidates for the therapy of Parkinson's disease (PD) for which can promote the survival of midbrain dopaminergic neurons. In addition to secret out from cells like other classical neurotrophic factors (NTFs), CDNF can locate in the endoplasmatic reticulum (ER), where they can function as ER stress response protein to regulate ER stress. In our previous studies, we have found two helices, a1 and a7, which can regulate the intracellular trafficking and secretion of CDNF. a1 distruction can significantly retain CDNF protein in the ER, but a7 distruction induce most CDNF protein secreting out the cells. Then a1 and a7 regulate protein trafficking and secretion in opposite side. However, the exact secretion level of CDNF affected by a1 or a7 have not been sensitively quantified. In this study, we used nanoluciferase to quantify the secretion level of CDNF protein so that we could evaluate the impact of a1 and a7 on CDNF secretion or function.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative analysis on secretion level of CDNF regulated by two key α‐helices in CDNF protein

Líu

Zhong

Zhao

et al. 2019

Cell Biology International

View full text Add to dashboard Cite

show abstract

“…Growth factors GDNF, CDNF, MANF, FGF2, brainderived neurotrophic factor (BDNF), epidermal growth factor (EGF) and heparin-binding epidermal growth factor (HB-EGF) were chosen for inclusion in this study based on reports demonstrating these factors to be neuroprotective or neurorestorative for dopaminergic neurons (9,17,20,21,34,36), or that these factors support learning and memory in animal models of AD (40,41,58,65,94). Hippocampal levels of these factors were quantified in ten cases of PD and nine age-matched normal controls.…”

Section: Methodsmentioning

confidence: 99%

Levels of glial cell line‐derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson’s disease

et al. 2019

Self Cite

View full text Add to dashboard Cite

Growth factors can facilitate hippocampus‐based learning and memory and are potential targets for treatment of cognitive dysfunction via their neuroprotective and neurorestorative effects. Dementia is common in Parkinson’s disease (PD), but treatment options are limited. We aimed to determine if levels of growth factors are altered in the hippocampus of patients with PD, and if such alterations are associated with PD pathology. Enzyme‐linked immunosorbent assays were used to quantify seven growth factors in fresh frozen hippocampus from 10 PD and nine age‐matched control brains. Western blotting and immunohistochemistry were used to explore cellular and inflammatory changes that may be associated with growth factor alterations. In the PD hippocampus, protein levels of glial cell line‐derived neurotrophic factor were significantly decreased, despite no evidence of neuronal loss. In contrast, protein levels of fibroblast growth factor 2 and cerebral dopamine neurotrophic factor were significantly increased in PD compared to controls. Levels of the growth factors epidermal growth factor, heparin‐binding epidermal growth factor, brain‐derived neurotrophic factor and mesencephalic astrocyte‐derived neurotrophic factor did not differ between groups. Our data demonstrate changes in specific growth factors in the hippocampus of the PD brain, which potentially represent targets for modification to help attenuate cognitive decline in PD. These data also suggest that multiple growth factors and direction of change needs to be considered when approaching growth factors as a potential treatment for cognitive decline.

show abstract

“…Intrastriatal injection of AAV‐CDNF has been shown to protect and recover 6‐OHDA‐induced behavioral deficits and to induce significant restoration of nigral DA neurons and their striatal fibres (Back et al., ; Ren et al., ). Following the positive outcomes in the studies on rodent models, a safety and efficacy study using chronic intrastriatal infusion of CDNF protein in 6‐OHDA‐lesioned marmosets (Garea‐Rodriguez et al., ) paved the way for clinical trials with this NTF.…”

Section: Trophic Factors In Preclinical Models Of Parkinson's Diseasementioning

confidence: 99%

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

Paul

Sullivan

2018

Eur J of Neuroscience

View full text Add to dashboard Cite

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.

show abstract

Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson’s Disease

Cited by 46 publications

References 74 publications

Quantitative analysis on secretion level of CDNF regulated by two key α‐helices in CDNF protein

Quantitative analysis on secretion level of CDNF regulated by two key α‐helices in CDNF protein

Levels of glial cell line‐derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson’s disease

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

Contact Info

Product

Resources

About