Mechanisms by which fibroblast growth factor 20 improves motor performance in a mouse model of Parkinson’s disease

Wang, Aiqin; Kong, Lina; Meng, Mingzhu; Chen, Si; Wang, Xiaotang

doi:10.4103/1673-5374.253527

Cited by 4 publications

(1 citation statement)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of these experimental models in PD has permitted the discovery of different therapeutic candidates, with different degree of evidence on their potential therapeutic activity and security concerns. This is the case of FGF20, echinacoside, rosmarinic acid or autophagic modulators, as Threalose or Torin 1, among many others, targeting different disrupted cell pathways in disease (Liang et al, 2019; Lv et al, 2019; Wang et al, 2019). Depending on the subtype of PD, specific treatments have been proposed.…”

Section: Disease Modifying Therapiesmentioning

confidence: 99%

Bioenergetics and Autophagic Imbalance in Patients-Derived Cell Models of Parkinson Disease Supports Systemic Dysfunction in Neurodegeneration

et al. 2019

View full text Add to dashboard Cite

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder worldwide affecting 2–3% of the population over 65 years. This prevalence is expected to rise as life expectancy increases and diagnostic and therapeutic protocols improve. PD encompasses a multitude of clinical, genetic, and molecular forms of the disease. Even though the mechanistic of the events leading to neurodegeneration remain largely unknown, some molecular hallmarks have been repeatedly reported in most patients and models of the disease. Neuroinflammation, protein misfolding, disrupted endoplasmic reticulum-mitochondria crosstalk, mitochondrial dysfunction and consequent bioenergetic failure, oxidative stress and autophagy deregulation, are amongst the most commonly described. Supporting these findings, numerous familial forms of PD are caused by mutations in genes that are crucial for mitochondrial and autophagy proper functioning. For instance, late and early onset PD associated to mutations in Leucine-rich repeat kinase 2 (LRRK2) and Parkin (PRKN) genes, responsible for the most frequent dominant and recessive inherited forms of PD, respectively, have emerged as promising examples of disease due to their established role in commanding bioenergetic and autophagic balance. Concomitantly, the development of animal and cell models to investigate the etiology of the disease, potential biomarkers and therapeutic approaches are being explored. One of the emerging approaches in this context is the use of patient’s derived cells models, such as skin-derived fibroblasts that preserve the genetic background and some environmental cues of the patients. An increasing number of reports in these PD cell models postulate that deficient mitochondrial function and impaired autophagic flux may be determinant in PD accelerated nigral cell death in terms of limitation of cell energy supply and accumulation of obsolete and/or unfolded proteins or dysfunctional organelles. The reliance of neurons on mitochondrial oxidative metabolism and their post-mitotic nature, may explain their increased vulnerability to undergo degeneration upon mitochondrial challenges or autophagic insults. In this scenario, proper mitochondrial function and turnover through mitophagy, are gaining in strength as protective targets to prevent neurodegeneration, together with the use of patient-derived fibroblasts to further explore these events. These findings point out the presence of molecular damage beyond the central nervous system (CNS) and proffer patient-derived cell platforms to the clinical and scientific community, which enable the study of disease etiopathogenesis and therapeutic approaches focused on modifying the natural history of PD through, among others, the enhancement of mitochondrial function and autophagy.

show abstract

Section: Disease Modifying Therapiesmentioning

confidence: 99%

Bioenergetics and Autophagic Imbalance in Patients-Derived Cell Models of Parkinson Disease Supports Systemic Dysfunction in Neurodegeneration

et al. 2019

View full text Add to dashboard Cite

show abstract

Positron emission tomography/computed tomography dual imaging using 18-fluorine flurodeoxyglucose and 11C-labeled 2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane for the severity assessment of Parkinson disease

Zhang²,

Qin³

et al. 2020

Medicine

View full text Add to dashboard Cite

The value of dual imaging mode for the severity assessment of Parkinson disease (PD) is explored by conducting positron emission tomography computed tomography (PET/CT) double imaging using combined 18-fluorine flurodeoxyglucose ( 18 F-FDG) brain metabolism and 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane ( 11 C-CFT) brain dopamine transporter (DAT). A total of 102 patients with PD and 50 healthy people in the control group are enrolled for the PET/CT dual imaging of 18 F-FDG brain metabolism and 11 C-CFT brain DAT. The characteristics of 18 F-FDG PET/CT and 11 C-CFT PET/CT imaging are analyzed by delineating the region of interest. Differences in the glucose metabolism and DAT distribution in the basal ganglia of patients with PD and healthy control group in the PET/CT imaging and the radioactive distribution characteristics of cerebral cortex in glucose metabolism imaging are compared. The characteristics of PET/CT imaging of 11 C-CFT brain DAT in the ganglion region in absorbing 11 C-CFT in different PD groups are analyzed. Compared with the healthy control group, changes in the cerebral glucose metabolism in the PD group mainly occur due to the increased symmetry metabolism of the nucleus of bilateral basal ganglia and the decreased metabolism of the cerebral cortex as shown in the 18 F-FDG PET/CT images. With disease progression, the bilateral parietal, frontal, temporal, and occipital leaves showed different degrees of FDG metabolism. Statistically significant difference is observed for the 11 C-CFT absorption among the caudate nucleus and the anterior, middle, and posterior nuclei of the bilateral basal ganglia of the PD and healthy control groups. In the PD group, the bilateral caudate nucleus and the anterior, middle, and posterior parts of the putamen show decreased DAT distribution. Regardless of unilateral or bilateral symptoms, the DAT distribution in the nucleus of the contralateral basal ganglia and in the posterior part of the nucleus is substantially reduced. PET/CT dual imaging by 18 F-FDG PET/CT combined with 11 C-CFT PET/CT features high application value for the severity assessment of PD.

show abstract

Designing Olfactory Ensheathing Cell Transplantation Therapies: Influence of Cell Microenvironment

et al. 2022

View full text Add to dashboard Cite

Olfactory ensheathing cell (OEC) transplantation is emerging as a promising treatment option for injuries of the nervous system. OECs can be obtained relatively easily from nasal biopsies, and exhibit several properties such as secretion of trophic factors, and phagocytosis of debris that facilitate neural regeneration and repair. But a major limitation of OEC-based cell therapies is the poor survival of transplanted cells which subsequently limit their therapeutic efficacy. There is an unmet need for approaches that enable the in vitro production of OECs in a state that will optimize their survival and integration after transplantation into the hostile injury site. Here, we present an overview of the strategies to modulate OECs focusing on oxygen levels, stimulating migratory, phagocytic, and secretory properties, and on bioengineering a suitable environment in vitro.

show abstract

Mechanisms by which fibroblast growth factor 20 improves motor performance in a mouse model of Parkinson’s disease

Cited by 4 publications

References 52 publications

Bioenergetics and Autophagic Imbalance in Patients-Derived Cell Models of Parkinson Disease Supports Systemic Dysfunction in Neurodegeneration

Bioenergetics and Autophagic Imbalance in Patients-Derived Cell Models of Parkinson Disease Supports Systemic Dysfunction in Neurodegeneration

Positron emission tomography/computed tomography dual imaging using 18-fluorine flurodeoxyglucose and 11C-labeled 2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane for the severity assessment of Parkinson disease

Designing Olfactory Ensheathing Cell Transplantation Therapies: Influence of Cell Microenvironment

Contact Info

Product

Resources

About