The Olfactory Receptor Pseudo-pseudogene: A Potential Therapeutic Target in Human Diseases

Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons （OSNs）f2J. Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechelfia Ir75a gene is generally recognized as a pseudogene in OSNs.

Substance P and its tachykinin NK1 receptor: a novel neuroprotective target for Parkinson's disease

Parkinson＇s disease （PD） is the most common motor neurode- generative disorder affecting approximately 4 million people worldwide. Although PD presents primarily with motor dysfunction, non-motor symptoms including cognitive decline, mood disorders, reduced olfaction and constipation are also of- ten present, with some of these non-motor symptoms even pre- senting prior to the onset of motor symptoms. It is well known that PD is largely caused by the gradual degeneration of dopa- minergic neurons within the substantia nigra pars compacta （SNc）, along with the presence of protein aggregates called Lewy bodies, which consist primarily of ct-synuclein and are found in the cytoplasm of surviving neurons. This ongoing cell loss and Lewy body pathology is not confined to the SNc, but is also seen in other brain regions implicated in PD pathogenesis such as the locus ceruleus.

The seeming paradox of adenosine receptors as targets for the treatment of Alzheimer's disease: agonists or antagonists?

Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatically （about 30%） in people aged 80 years or older （Selkoe, 2002）. Nowadays, considering the increasing mean lifespan of populations in developed countries, the disease is becoming more and more a health concern, and the search for an effective cure has turned into＂a real need＂.

Histone methylation in Huntington's disease:are bivalent promoters the critical targets?

Huntington’s disease（HD）is a currently incurable,late onset,progressive,ultimately fatal neurological disorder（Bates et al.,2015）.We have recently published the results of comprehensive genetic interaction tests aimed at identification of histone methyltransferases and demethylases involved in HD pathogenesis in a Drosophila model of the disease（Song et al.,2018）.

Is it time to rethink the Alzheimer's disease drug development strategy by targeting its silent phase?

Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.

Targeting the guanine-based purinergic system in Alzheimer's disease

Alzheimer’s disease（AD）is the main cause of dementia worldwide and affects approximately 5%of people with 65 years or older.The estimated increase in the elderly population suggests that cases of AD will rise in the next years.

SLP-2: a potential new target for improving mitochondrial function in Parkinson's disease

Parkinson＇s disease （PD） is a progressive neurodegenerative disease, which is generally considered a multifactorial disorder that arises owing to a combination of genes and environmental factors. While most cases are idiopathic, in about 10% of the patients a genetic cause can be detected, ascribable to mutations in more than a dozen genes. PD is characterized clinically by tremor, rigidity, reduced mo- tor activity （bradykinesia）, and postural instability and pathological- ly by loss of dopaminergic （DA） neurons in the substantia nigra pars compacta, loss of DA innervation in the striatum, and the presence of a-synuclein positive aggregates in the form of Lewy bodies. The symptomatic treatment of PD with levodopa, which aims at replac- ing dopamine, remains the gold standard, and no neuroprotective or disease-modifying therapy is available. During treatment, the disease continues to progress, and long-term use of levodopa has import- ant limitations including motor complications termed dyskinesias. Therefore, a pharmacological therapy able to prevent or halt the neu- rodegenerative process is urgently required.

Targeting Ageing to Decrease Complex Non-Communicable Human Diseases

During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many people died before reaching adult- hood, nowadays most people survive. Hence average life ex- pectancy in 1800s was around 30-40, which was barely higher than it had been in Greek and Roman times （Finch, 2010）, but nowadays life expectancy in most modernised economies is around 75 - 80. This demographic shift, which has happened in only 200 years, has created a dramatic change in the causes of mortality. The major killers in the modern world are non- communicable diseases （NCDs）： principally cardiovascular disease, cancer and neurodegenerative disorders such as Alz- heimer＇s disease. A major factor that influences susceptibility to all these diseases is age. As we get older, our risk of developing these NCDs increases enormously. For example, the rate of breast cancer in females at age 15-19 is less than 10 per 100,000 population, but this increases to 100 at age 40-44, 275 at age 55--59 and 450 at age 85 ＋ （http：//www.cancerresearchuk.org/ cancer-info/cancerstats/types/breast/incidence/#age）. Ageing has consequently become a major medical, social and economic burden to many countries.

Exploring Traditional Chinese Medicine by A Novel Therapeutic Concept of Network Target

Traditional Chinese medicine（TCM） holds a holistic theory, and specializes in balancing disordered human body using numerous natural products, particularly Chinese herbal formulae. TCM has certain treatment advantages for patients suffering from various complex diseases. However, due to the complex nature of TCM, it remains difficult to unveil such holistic medicine by the current reductionism research strategies, which treat both herbal ingredients and targets in isolation. Recently, an emerging network pharmacology approach has been introduced to tackle this bottleneck problem. A TCM-derived novel therapeutic concept, ＂network target＂, which is different from the Western medicine＇s ＂onetarget＂ concept, has been proposed from China. The network target strategy is able to illustrate the complex interactions among the biological systems, drugs, and complex diseases from a network perspective, and thus provides an innovative approach to access ancient remedies in a precision manner and at a systematic level, which also highlights TCM＇s potential in current medical systems.

The Mitochondrion:A Potential Therapeutic Target for Alzheimer's Disease

Introduction The mitochondrion is a double-membrane organelle consisting of an outer membrane, intermembrane space, inner membrane, cristae, and matrix. It is the ‘‘energy plant’’ that provides most of the energy for cells. Mitochondria also participate in various processes such as calcium homeosta-

The clinical and genetic characteristics in children with mitochondrial disease in China

Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing(NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children's Hospital, Capital Medical University from October 2012 to January 2015. In our study, 40 cases of gene confirmed mitochondrial disease including eight kinds of mitochondrial disease, among which Leigh syndrome was identified to be the most common type, followed by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS). The age-of-onset varies among mitochondrial disease, but early onset was common. All of 40 cases were gene confirmed, among which 25 cases(62.5%)with mitochondrial DNA(mtDNA) mutation, and 15 cases(37.5%) with nuclear DNA(nDNA) mutation. M.3243A>G(n=7)accounts for a large proportion of mtDNA mutation. The nDNA mutations include SURF1(n=7),PDHA1(n=2),and NDUFV1,NDUFAF6, SUCLA2, SUCLG1, RRM2 B, and C12orf65, respectively.