Neurodegenerative diseases represent a significant unmet medical need in our aging society. There are no effective treatments for most of these diseases, and we know comparatively little regarding pathogenic mechanisms. Among the challenges faced by those involved in developing therapeutic drugs for neurodegenerative diseases, the syndromes are often complex, and small animal models do not fully recapitulate the unique features of the human nervous system. Human induced pluripotent stem cells (iPSCs) are a novel technology that ideally would permit us to generate neuronal cells from individual patients, thereby eliminating the problem of species-specificity inherent when using animal models. Specific phenotypes of iPSC-derived cells may permit researchers to identify sub-types and to distinguish among unique clusters and groups. Recently, iPSCs were used for drug screening and testing for neurologic disorders including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), spinocerebellar atrophy (SCA), and Zika virus infection. However, there remain many challenges still ahead, including how one might effectively recapitulate sporadic disease phenotypes and the selection of ideal phenotypes and for large-scale drug screening. Fortunately, quite a few novel strategies have been developed that might be combined with an iPSC-based model to solve these challenges, including organoid technology, single-cell RNA sequencing, genome editing, and deep learning artificial intelligence. Here, we will review current applications and potential future directions for iPSC-based neurodegenerative disease models for critical drug screening.

Hippocampus is one of the most vulnerable brain regions in terms of age-related pathological change. Exercise is presumed to delay the aging process and promote health because it seems to improve the function of most of the aging mechanisms. The purpose of this study is to evaluate the effects of swimming exercise training on brain inflammation, apoptotic and survival pathways in the hippocampus of D-galactose-induced aging in SD rats. The rats were allocated to the following groups: (1) control; (2) swimming exercise; (3) induced-aging by injecting Dgalactose; (4) induced-aging rats with swimming exercise. The longevity-related AMPK/SIRT1/PGC-1α signaling pathway and brain IGF1/PI3K/Akt survival pathway were significantly reduced in D-galactose-induced aging group compared to non-aging control group and increased after exercise training. The inflammation pathway markers were over-expressed in induced-aging hippocampus, exercise significantly inhibited the inflammatory signaling activity. Fas-dependent and mitochondrial-dependent apoptotic pathways were significantly increased in the induced-aging group relative to the control group whereas they were decreased in the aging-exercise group. This study demonstrated that swimming exercise not only reduced aging-induced brain apoptosis and inflammatory signaling activity, but also enhanced the survival pathways in the hippocampus, which provides one of the new beneficial effects for exercise training in aging brain.

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The integration of traditional Chinese and Western medicine and their clinical effects have been widely evaluated. Many studies have shown that using a combination of these two remedies has resulted in better outcomes than using only one of them. Acupuncture is a traditional Chinese medical technique, which plays an important role in enforcing pain control, prevention and functional improvement. In 1979, the World Health Organization (WHO) journal introduced acupuncture as a remedy for 43 diseases, including frozen shoulder. This study aims to assess the therapeutic outcomes of combining acupuncture and physical therapy to treat frozen shoulder, and hopes to establish an evidence-based study of the integration of acupuncture and western medicine in the future. A total of 75 frozen shoulder patients treated in a medical center were recruited for the study between January 2002 and December 2002. The average age of these patients was 54.8 years. The average duration of the condition was 25.8 weeks before treatment. Of the 75 patients, 30 were treated by physical therapy, 30 by acupuncture and 15 by both remedies. Before the treatment began, all patients were evaluated by assessing static pain scale, motion pain scale, active and passive ROM (range of motion) and quality of life scale sheet SF-36 (Short Form-36). The outcome was evaluated by follow-up assessments conducted at the 2nd week and 4th week of treatment sessions. All patients showed improvement in quality of life (Short Form-36). Pain was controlled better by acupuncture while ROM improved following physical therapy. However, patients treated by both methods had the best outcome. The integration of acupuncture and physical therapy to treat frozen shoulder leads to a better outcome than using only one method. The author suggests that an evidence-based foundation of the integration of Chinese and Western medicine should be established in the future, to encourage the integration of Chinese and Western medicine.