Parkinson′s disease(PD),the second neurodegenerative disease in the world,is characterized by a combination of motor symptoms(rest tremor,bradykinesia,rigidity,postural instability,stooped posture and freezing of gait)and non-motor symp?toms(including psychiatric and cognitive disorders). The core neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra and the deposition of iron and cytoplasmic protein aggregates(Lewy bodies)inside neurons. Currently,clinical treatment for PD is symptomatic and there is no effective treatment to restore neuronal degeneration. In the PD therapy ,medication re?mains dominant. Anti-PD drugs are mainly based on the critical signal pathways or some specific targets which play a key role in the pathogenesis of PD to relieve the symptoms of PD. Research and development in novel drugs to prevent or treat PD have been a crucial subject,and some novel candidates are under development. In this paper,we summarize and analyze the anti-PD drugs,and make a brief discussion about its pharmacological targets.

Luteinizing hormone(LH)is a gonadotropin of hypothalamic-pituitary-gonadal axis(HPG),secreted by the anteri?or pituitary. The secretion of LH is directly controlled by the release of gonadotropin releasing hormone(GnRH),acts at the ovaries and testes to stimulate the production of gonadal hormones. Aging leads to increases in LH,and higher serum levels of LH has been ob?served in Alzheimer′s disease(AD)patients when compared to age-matched controls. Evidences from basic research and epidemiologi?cal investigation support the critical role of elevated LH in pathogenic process of AD and deteriorating cognitive decline. Here we sum?marize the recent discoveries containing human AD epidemiological evidence for LH,cognitive impairments resulting from LH activi?ty,LH in AD pathology and LH receptor signaling mechanisms.

Alzheimer′s disease(AD)is one of the most common causes of cognitive impairment.“Aβhypothesis”and“tau protein aggregation hypothesis”are two representative hypotheses in relation to AD pathology. But recently,therapeutic strategy target?ing on reducing Aβdeposition failed in clinical trials. On the other hand,as the phosphorylation of tau protein is regulated by multiple upstream kinases,inhibition of a single kinase usually cannot effectively suppress the aggregation of the tau. While blocking multiple kinases at the same time will produce serious side effects. Currently,targeting on Aβand tau protein get into awkward situations. In view of this,researchers are looking for new drug targets for improving cognitive function. Phosphodiesterase 4(PDE4 4)is an enzyme responsible for the hydrolysis of cAMP in the body. There are four subtypes for PDE4,and PDE4A,B and D are highly expressed in the central nervous system. Inhibition of PDE4 causes activation of cAMP/PKA/CREB/BDNF signal pathway,which is beneficial for the strengthening and consolidation of learning and memory. This review will focus on the most recent evidence regarding the role of PDE4 in learning and memory.

Protein phosphatase 2A(PP2A)is the main serine/threonine protein phosphatase of the brain,and it is involved in many physiological and pathological processes in the cell. Particularly in the pathogenesis of Alzheimer′s disease(AD),PP2A is closely related to the main pathological features of AD. Deregulation of PP2A enzymes correlates with increased tau phosphorylation, the formation of amyloid precursor protein,and the missing of neurons. PP2A as the target of drug development may bring new hope for the treatment of AD. This review introduces the structure and activity regulation of PP2A,and the role of PP2A in AD.

Rho/ROCK pathway is a ubiquitous singling pathway in organisms,and is involved in many biological processes. In the brain of Alzheimer′s patients,the activities of Rho and Rho associated coiled coil forming protein kinase(ROCK)are up-regulat?ed,which is accompanied by the elevation of Aβ42 level,and the abnormal change of the morphology and function of neuronal process?es,suggesting that the occurrence and development of Alzheimer′s disease(AD)is associafed with the overexpression and excessive activation of Rho or ROCK. Rho/ROCK2 pathway is considered a target pathway for the prevention and treatment of AD,and Rho or ROCK2 also becomes an important target for AD drug development. Numerous studies have revealed that suppressing the expression or decreasing the activity of Rho or ROCK2 can reduce Aβ42-induced neurotoxicity,protect neurons,and slow down the occurrence and de?velopment of AD. Therefore,specific inhibition of ROCK2 has an important significance for the repair of central nervous system dam?age and the treatment of AD. This article reviews several effects of Rho/ROCK2 pathway on the development of AD.

Alzheimer′s disease(AD)is a degenerative metabolic disease,whose exact pathological mechanism still remains unknown. Currently,studies have found that patients in AD accompany with insulin signaling pathway impairment and cerebral glu?cose metabolism dysfunction. As insulin signaling pathway and cerebral glucose metabolism homeostasis play a key role in AD ,some researches consider AD as“typeⅢdiabetes”. This review aims to discuss the alteration of cerebral insulin signaling pathway and glu?cose metabolism in AD,as well as their relationship with AD. We will also elaborate the advance in anti-AD drugs based on cerebral insulin signaling pathway.

Alzheimer′s disease(AD)is a neurodegenerative disorder resulted from complicate interactions between genes and environment. There is no effective therapy so far. The genome-wide association study(GWAS)provides the opportunity to discover the risk genes of sporadic AD,which is informative for revealing the pathogenesis of AD and guiding new drug development. In this re?view,we summarize the current findings of genetic studies of AD,the risk genes and their biological relevance with AD,and new drug development strategy supported by genetic studies.

Alzheimer′s disease(AD)is a major form of neurodegenerative disease. Due to the lack of effective treatment for AD,drug discovery is imminent,and genomics has become a driving force for the drug discovery. Genomic studies of AD involve sever?al aspects,such as large-scale studies on the genetic risk,brain transcriptome studies,and epigenetic studies. Notable progress has been made in genomic studies of AD,which has facilitated the drug discovery. In the meantime,biomarkers for early diagnosis includ?ing those from peripheral blood have emerged as a major research topic because early detection and intervention are the prominent task for the moment. Research progress in this field will be briefly reviewed. Because of the vast heterogeneity in AD pathogenesis ,genom?ics will also provide strong support for precision medicine in the future.

Zika virus(ZIKA),a member of the Flaviviridae family,was discovered serendipitously in 1947 in the Zika forest of Uganda. In May 2015,the Pan American Health Organization(PAHO)issued an alert regarding the first confirmed Zika virus infec? tion in Brazil. Recently,the virus has been tentatively linked to a severe neurodevelopmental birth defect known as microcephaly in in? fants born to mothers who were infected during pregnancy. The virus has gradually become the hot spot in international medical re? search. The health authorities are calling for the rapid development of diagnostics,vaccines and antiviral drugs.

PD-1/PD-L1 signaling pathway as a T cell immune response co-stimulatory signaling pathway plays an important role in adaptive immunity. PD-1 is a major co-receptor expressing on T cells, binding with its ligands(PD-L1 and PD-L2), PD-1 can inhibit T cell activation and protect the body against the attacks from its own immune system. In addition to adjusting and maintaining autoimmune tolerance, in tumor cells PD-L1 expression is up-regulated, while in the virus-infected T cells PD-L1 expression is also upregulated. PD-1 / PD-L1 are involved in the tumor and infectious pathogen immune evasion, thus blocking the PD-1 / PD-L1 signaling pathway has become a hot research of cancer and chronic diseases. Currently, there are several anti-PD-1 or PD-L1 monoclonal antibodies approved by the FDA to enter clinical studies, which have shown significant anti-cancer effect.