Narrow Results

Expatriate Researcher Returns to Roost.

Past, Present and Future of Stem Cells in Regenerative Medicine.

Learning Human Cardiac Diseases through Stem Cells.

Bioprocessing for Stem Cell Therapy: From the Lab into the Log Phase.

Neural Stem Cells and Cell-based Approaches in Neurodegeneration and Peripheral Nerve Injuries.

The Marketing of Unapproved Stem Cell Products: An Industry-wide Challenge.

AUSTRALIA – Malaria transmission-blocking vaccines to be developed.

MALAYSIA – Dengue vaccine is just a year away, researchers say.

SINGAPORE – Molecular test kit to predict survival options in kidney cancer.

SINGAPORE – A*STAR scientists make breakthroughs in ovarian cancer research.

SINGAPORE – MicroVax cancer vaccine first in human clinical trial in Singapore.

AFRICA – Mixed results for yellow cassava's vitamin A trial.

AFRICA – GM's potential in Africa impeded by ‘dysfunctional debate’.

BRAZIL – Cheap nasal spray may save snakebite victims.

EUROPE – Promising next generation drug treatment for malaria developed.

EUROPE – Network Verification Challenge generates COPD network models.

EUROPE – Merck Serono initiates phase II study of antibody in metastatic merkel cell carcinoma.

UNITED STATES – Discovery of pro-metastasis protein reveals mysterious link to neurodegeneration.

UNITED STATES – Biologists discover mechanism promoting multiple DNA mutations.

SINGAPORE – VIVA Foundation and NUS Launches $10 Million Cancer Research Centre for Childhood Leukaemia.

SINGAPORE – Discovery Paves the Way for Potential Genetics-Guided Precision Medicine for Paediatric Leukaemia Patients.

SINGAPORE – Partnership between Sony and Alder Hey Children's Hospital Drives Innovation in Children's Healthcare.

UNITED STATES – UGA Researchers Make Link between Genetics and Aging.

UNITED STATES – Latin Dancing may Have Health Benefits for Older Adults.

UNITED STATES – Interferon Not Beneficial for Most Stage III Melanoma.

UNITED STATES – Dissecting the Animal Diet, Past and Present.

UNITED STATES – Water Conservation Important to Many; Only Some Take Action.

UNITED KINGDOM – Innova Biosciences Introduces New LATEX One-Step Conjugation Kits.

UNITED KINGDOM – New Understanding of the Mechanism of Neurodegeneration Leads to a Novel Approach to Treatment for Alzheimer's Disease.

TAIWAN – Breakthrough in Homogeneous Antibody Development and a New Generation of Glycoarray Technology.

TAIWAN – Increasing Protein Synthesis by Leucine Ameliorates Synaptopathy Caused by Dementia, ALS and Autism.

SINGAPORE – A New Way of Looking at Cancer

SINGAPORE – Novel Discovery by NUS Scientists Improves Profiling of AML Patients for Targeted Therapies

SINGAPORE – Red Meat Consumption Linked with Increased Risk of Developing Kidney Failure

SINGAPORE – Thomson Medical and UK-based Cell Therapy Limited Collaborate on Stem Cell Research to Develop Regenerative Medicines

UNITED STATES – New Biomaterial Developed for Injectable Neuronal Control

UNITED STATES – Research Shines Light on Lesser Known Form of Vitamin D in Foods

UNITED STATES – MRIGlobal to Lead International Research Collaboration for Tularemia Vaccine

INDIA – Improving Agricultural Yield and Quality through Tissue Culture Technology

TAIWAN – A Cascade of Protein Aggregation Bombards Mitochondria for Neurodegeneration and Apoptosis under WWOX Deficiency

For the month of October 2021, APBN explores astrobiology and the planetary sciences. In Features, we look into the age-old question: are we alone in the Universe? If not, how might life emerge elsewhere in the Cosmos and taking what we know now, where do we go from here? Then we have a special contribution by Professor Chandra Wickramasinghe, astronomer and pioneer of astrobiology, who discusses the Panspermia theory and the role of culture in delaying the acceptance of the theory. In Columns, we review the latest human gene therapy trials using adeno-associated viruses as vectors to treat neurodegenerative disorders. Finally, in Spotlights, we share highlights from a conference by SGInnovate and CATALYST potential of bioprinting in personalised medicine and an interview with Dr. Senthil Sockalingam, Head of IQVIA Biotech, JAPAC & Chief Medical Officer, APAC, on its expansion in the Asia-Pacific and how the company's new innovative approach will utilise data and analytics to accelerate clinical development.

For the months of May and June 2022, APBN some of the cutting-edge research in cell and molecular biology that are helping us pave the way towards a healthier future. In Features, we have Dr Matthew Moulton and Dr Hugo Bellen from the Bellen Lab on the novel links between Alzheimer's disease risk genes and the build-up of lipids due to mitochondrial dysfunction, Dr Ross Macdonald, Managing Director and Chief Executive Officer at Cynata Therapeutics, on stem cell technology and the different clinical trials underway at Cynata, Vanessa Lunardi on age-related macular degeneration and the potential treatments we can look forward to in the future, and Liz Henderson, Regional Vice President, Asia-Pacific Region at Merck Healthcare, on cancer preparedness in emerging markets.

In Columns, Hamish Thrum, Senior Director of Myopia Asia Pacific at CooperVision sheds some light on myopia in Asia and calls for the implementation of standard of care in treating myopia, Dr Gajendra Singh, Public Health Consultant, shares some challenges and solutions to drive vaccine access, Dr Rebecca Dent, Senior Consultant at National Cancer Center Singapore, highlights the importance of medical innovation to enhance patients’ access to better cancer drugs, and Jennifer Cho, Vice President & Managing Director of Singapore/Malaysia sub-region at Medtronic, with how artificial intelligence can improve cancer management.

In Spotlights, we speak to Dr Ronald Ling, Chief Executive Officer at ConnectedHealth, on how we may utilise technology to better manage diabetes, and Dr Ellis Douek, a cochlear implant pioneer, as he shares his life as an Ear, Nose & Throat surgeon.

A computation approach to identify the effect of missense mutations on the protein function is proposed. Using molecular dynamics simulation we have analyzed the gating kinetics of mutant NMDA synaptic receptors carrying mutations in their NR2 subunits. Analysis of channel geometry and Mg ion binding allowed to estimate the receptor conductivity. As a result, it was possible to identify the effect of these mutations on the generation of theta and gamma rhythms by the hippocampal neural network. Obtained results can be adapted for the analysis and evaluation of possible cognitive impairments caused by neurological diseases or consequences of radiation and other negative factors.

Impressive progress has been made in clinical development of adeno-associated virus (AAV) vectors over the last 15 years in more than 40 clinical trials, involving many hundreds of subjects with vector delivery by many different routes and at a wide range of doses. Preclinical expectations, including an excellent safety profile, the tendency to remain at a local delivery site, and the persistence of expression for years after delivery, are being borne out in clinical trials. Immune responses to the vectors in human subjects, less well anticipated by preclinical studies, are now being examined in current AAV vector clinical trials, in order to determine in what circumstances such responses might occur or be problematic. Development of AAV vectors is likely to continue to be an expanding field. The current successes in the subjects with retinal degeneration and Parkinson's disease are highly encouraging for AAV vectors and for the whole field of gene therapy.

A recent large genome-wide association meta-analysis revealed that the human WWOX gene is regarded as one of the five newly identified risk factors for Alzheimer’s disease (AD). However, this study did not functionally characterize how WWOX protein deficiency affects AD initiation, progression and neurodegeneration. In this review, evidence and perspectives are provided regarding how WWOX works in limiting neurodegeneration. Firstly, loss of WWOX/Wwox gene leads to severe neural diseases with degeneration, metabolic disorder and early death in the newborns. Downregulation of pY33-WWOX may start at middle ages, and this leads to slow aggregation of a cascade of proteins, namely TRAPPC6A$\mathrm{\Delta }$, TIAF1 and SH3GLB2, that leads to amyloid-beta (A$\beta$) formation and tau tangle formation in old-aged AD patients. Secondly, functional antagonism between tumor suppressors p53 and WWOX may occur in vivo, in which p53-mediated inflammation is blocked by WWOX. Loss of balance in the functional antagonism leads to aggregation of pathogenic proteins for AD such as tau and A$\beta$ in the brain cortex and hippocampus. Thirdly, downregulation of pY33-WWOX is accompanied by upregulation of pS14-WWOX. The event frequently correlates with enhanced AD progression and cancer cell growth in vivo. A small peptide Zfra4-10 dramatically suppresses pS14-WWOX and restores memory loss in triple transgenic (3xTg) mice, and inhibits cancer growth in mice as well. Finally, a supporting scenario is that WWOX deficiency induces enhanced cell migration and loss of cell-to-cell recognition. This allows the generation of neuronal heterotopia and associated epileptic seizure in WWOX-deficient newborn patients.

Although metallothioneins (MTs) were discovered nearly 40 years ago, their functional role has still not been completely clarified. The role of MTs in the central nervous system has in particular become an intense focus of scientific research. Many papers have confirmed the active and peculiar role played by these proteins in neurodegenerative disorders, even if contrasting results are still present. The involvement of MTs in various neurodegenerative diseases (Alzheimer's disease, frontotemporal dementia, Binswanger's disease, Parkinson's disease, amyotrophic lateral sclerosis, and prion protein disease) is herein reported.

Zinc is relevant to the maintenance of brain functions. It is involved in glutaminergic transmission in the gene expression of transcriptional factors and in nerve growth factor activity. Zinc turnover in the brain is mediated by metallothionein (MT) and the zinc traffic into the brain is due to ZnTl-4 transporter proteins. Alterations in zinc turnover lead to brain dysfunction. During aging, zinc turnover is altered, coupled with decreased brain functions and impaired cognitive performances. This decrease may lead to neurodegeneration. One of the causes of altered zinc turnover in aging may be due to altered zinc-bound MT homeostasis, which transforms from being a protective shield against stress into a harmful factor in aging because of the exclusive sequestration of zinc and lack of subsequent zinc release by MT for brain functions. The beneficial effect of zinc supplementation is discussed in aging and neurodegeneration.

The prion protein, PrP^C, is a neuronal cell surface glycoprotein. In an abnormal isoform, termed PrP^Sc, it is associated with the family of neurodegenerative conditions called prion diseases. PrP^C was recently shown to bind copper and there is strong evidence that it has a role in the regulation of brain copper metabolism. Its expression alters copper uptake into cells and enhances copper incorporation into superoxide dismutase enzymes. Also, PrP^C has a superoxide dismutase-like function and may, therefore, protect neurons from the onslaught of reactive oxygen species. Furthermore, several lines of evidence have suggested that copper ions play a role in the biology of both PrP^C and PrP^Sc and may influence the conversion of PrP^C to PrP^Sc. This chapter provides an overview of the latest findings in this field and discusses structural and functional aspects of the prion protein.

Iron-related pathology is present in many neurodegenerative diseases, and the effects of iron mismanagement can serve as either primary or secondary causes of neurodegeneration. There are many mechanisms by which iron mismanagement can precipitate neurodegeneration, including misregulation of iron import and export, iron deficiency or accumulation, and oxidative damage resulting from loss of iron homeostasis. While the crucial role of iron in neurodegeneration is, in general, beginning to be appreciated, the mechanisms by which loss of iron homeostasis in the brain occurs are still unclear and questions regarding opportunities for therapeutic intervention involving iron chelation remain unanswered.

Parkinson's disease is a common neurodegenerative disorder characterized clinically by motor dysfunction. The primary pathological changes in the Parkinsonian brain are the degeneration of pigmented dopaminergic neurons of the substantia nigra and the development of pathological inclusions called Lewy bodies. Progressive cell loss in Parkinson's disease is suggested to result from self-sustaining mechanisms related to oxidative mechanisms and mitochondrial dysfunction. A common factor linking oxidative damage, mitochondrial dysfunction, and the development of Lewy bodies in Parkinson's disease is the presence of a significant and pathological increase in the amount of iron in the degenerating substantia nigra. The role of iron in biochemical pathways proposed to mediate these mechanisms and their association with the etiology of Parkinson's disease is discussed.

While clinical neurotoxicity of metals rarely results in neurodegeneration, the pathophysiology of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis is characterized by the accumulation of certain metal ions in the central nervous system, which eventually leads to free radical-mediated oxidative stress and neuronal death. However, it is not clear if metal accumulation is a primary or secondary event, whether it is pivotal in driving the progression of the disease, and how it may interact with genetic factors. Example only one suggests analogies between clinical neurotoxicity of metals and neurodegenerative diseases. Clinical, histopathological, and toxicological characteristics of manganese poisoning overlap with those of two metal accumulation diseases, Wilson's disease and Hallervorden-Spatz disease. The understanding of mechanistic analogies and differences among toxic and nontoxic diseases may help to clarify the role of metal accumulation in neurodegeneration.

People in different societies have known tremendous of indigenous medicinal plants since prehistoric time. Among these societies, Chinese people have discovered thousands plants of medicinal properties since thousands of years. They have used them in their food and prescriptions to invigorate their body functions and to treat different ailments, respectively. Since the middle of last century, great attention has been paid globally to medicinal plants trying to use their active ingredients as an alternative medicine. During this period, many molecular ingredients have been identified and isolated from these plants by the aid of modern analytical tools. More recently, some of these molecular substances have been shown to exert neuroprotective effects against a number of neurodegenerative disorders by modulating certain CNS targets. This chapter will address and discuss the effect of the most popular Chinese herbs and their active ingredients against age-related neurodegenerative diseases with special references to Alzheimer's and Parkinson diseases.