Research advances on antioxidation,neuroprotection,and molecular mechanisms of Lycium barbarum polysaccharides

Lycium barbarum polysaccharides(LBPs)are the major polysaccharides extracted from L.barbarum,which is used in traditional Chinese medicine(TCM)for treating diseases.Studies have shown that LBPs have important biological activities,such as antioxidation,anti-aging,neuroprotection,immune regulation.LBPs inhibit oxidative stress,improve neurodegeneration and stroke-induced neural injury,increase proliferation and differentiation of neural stem cell,and promote neural regeneration.Here we have reviewed latest advances in the biomedical activities of LBPs and improved methods for the isolation,extraction,and purification of LBPs.Then,new discoveries to decrease oxidative stress and cellular apoptosis,inhibit aging progress,and improve neural repair in neurodegeneration and ischemic brain injury have been discussed in detail through in vitro cell culture and in vivo animal studies.Importantly,the molecular mechanisms of LBPs in playing neuroprotective roles are further explored.Lastly,we discuss the perspective of LBPs as biomedical compounds in TCM and modern medicine and provide the experimental and theoretical evidence to use LBPs for the treatment of aging-related neurological diseases and stroke-induced neural injuries.

Development of stem cell-based therapy for Parkinson’s disease

Parkinson’s disease(PD)is one of the most common neurodegenerative disorders of aging,characterized by the degeneration of dopamine neurons(DA neurons)in the substantial nigra,leading to the advent of both motor symptoms and non-motor symptoms.Current treatments include electrical stimulation of the affected brain areas and dopamine replacement therapy.Even though both categories are effective in treating PD patients,the disease progression cannot be stopped.The research advance into cell therapies provides exciting potential for the treatment of PD.Current cell sources include neural stem cells(NSCs)from fetal brain tissues,human embryonic stem cells(hESCs),induced pluripotent stem cells(iPSCs)and directly induced dopamine neurons(iDA neurons).Here,we evaluate the research progress in different cell sources with a focus on using iPSCs as a valuable source and propose key challenges for developing cells suitable for large-scale clinical applications in the treatment of PD.

The application of patient-derived induced pluripotent stem cells for modeling and treatment of Alzheimer’s disease

Alzheimer’s disease(AD)is the most prevalent age-related neurodegenerative disease which is mainly caused by aggregated protein plaques in degenerating neurons of the brain.These aggregated protein plaques are mainly consisting of amyloidβ(Aβ)fibrils and neurofibrillary tangles(NFTs)of phosphorylated tau protein.Even though the transgenic murine models can recapitulate some of the AD phenotypes,they are not the human cell models of AD.Recent breakthrough in somatic cell reprogramming made it available to use induced pluripotent stem cells(i PSCs)for patientspecific disease modeling and autologous transplantation therapy.Human i PSCs provide alternative ways to obtain specific human brain cells of AD patients to study the molecular mechanisms and therapeutic approaches for familial and sporadic forms of AD.After differentiation into neuronal cells,i PSCs have enabled the investigation of the complex aetiology and timescale over which AD develops in human brain.Here,we first go over the pathological process of and transgenic models of AD.Then we discuss the application of i PSC for disease model and cell transplantation.At last the challenges and future applications of i PSCs for AD will be summarized to propose cell-based approaches for the treatment of this devastating disorder.

Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson's disease

Objective: Parkinson's disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.