Androgenetic alopecia occurs in men and women, and is characterised by the loss of hair from the scalp in a defined pattern. Determining factors appear to be genetic predisposition coupled with the presence of sufficient circulating androgens. The prevalence of this condition is high (up to 50% of white males are affected by 50 years of age) and, although there are no serious direct health consequences, the loss of scalp hair can be distressing. Knowledge of the pathogenesis of androgenetic alopecia has increased markedly in recent years. Pre-programmed follicles on the scalp undergo a transformation from long growth (anagen) and short rest (telogen) cycles, to long rest and short growth cycles. This process is coupled with progressive miniaturisation of the follicle. These changes are androgen dependent, and require the inheritance of several genes. To date, only one of these genes, which encodes the androgen receptor (AR), has been identified. Of the many treatments available for androgenetic alopecia, only two (finasteride and minoxidil) have been scientifically shown to be useful in the treatment of hair loss. However, these therapies are variable in their effectiveness. Discovery of the involvement of the AR gene, and the identification of other genes contributing to the condition, might lead to the development of new and more effective therapies that target the condition at a more fundamental level.

There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders characterised by long incubation period, short clinical duration, and transmissibility to susceptible species. Neuronal loss, spongiform changes, gliosis and the accumulation in the brain of the misfolded version of a membrane-bound cellular prion protein (PrPC), termed PrPTSE, are diagnostic markers of these diseases. Compelling evidence links protein misfolding and its accumulation with neurodegenerative changes. Accordingly, several mechanisms of prion-mediated neurotoxicity have been proposed. In this paper, we provide an overview of the recent knowledge on the mechanisms of neuropathogenesis, the neurotoxic PrP species and the possible therapeutic approaches to treat these devastating disorders.

In recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. Hendra and Nipah viruses (henipaviruses within this family) were first identified in the 1990s in Australia, Malaysia and Singapore, causing epidemics with high mortality and morbidity rates in affected animals and humans. Other paramyxoviruses, such as Menangle virus, Tioman virus, human metapneumovirus and avian paramyxovirus 1, which cause less morbidity in humans, have also been recently identified. Although the Paramyxoviridae family of viruses has been previously recognised as biomedically and veterinarily important, the recent emergence of these paramyxoviruses has focused our attention on this family. Antiviral drugs can be designed to target specific important determinants of the viral life cycle. Therefore, identifying and understanding the mechanistic underpinnings of viral entry, replication, assembly and budding will be critical in the development of antiviral therapeutic agents. This review focuses on the molecular mechanisms discovered and the antiviral strategies pursued in recent years for emerging paramyxoviruses, with particular emphasis on viral entry and exit mechanisms.

Amyotrophic lateral sclerosis (ALS) is a severe neuromuscular disease characterised by a progressive loss of motor neurons that usually results in paralysis and death within 2 to 5 years after disease onset. The pathophysiological mechanisms involved in ALS remain largely unknown and to date there is no effective treatment for this disease. Here, we review clinical and experimental evidence suggesting that dysregulation of copper homeostasis in the central nervous system is a crucial underlying event in motor neuron degeneration and ALS pathophysiology. We also review and discuss novel approaches seeking to target copper delivery to treat ALS. These novel approaches may be clinically relevant not only for ALS but also for other neurological disorders with abnormal copper homeostasis, such as Parkinson's, Huntington's and Prion diseases.

Genetic characterization of individuals at risk of Alzheimer's disease (AD), i.e. people having amyloid deposits in the brain without symptoms, people suffering from subjective cognitive decline (SCD) or mild cognitive impairment (MCI), has spurred the interests of researchers. However, their pre-dementia genetic profile remains mostly unexplored. In this study, we reviewed the loci related to phenotypes of AD, MCI and SCD from literature and performed the first meta-analyses evaluating the role of apolipoprotein E (APOE) in the risk of conversion from a healthy status to MCI and SCD. For AD dementia risk, an increased number of loci have been identified; to date, 28 genes have been associated with Late Onset AD. In MCI syndrome, APOE is confirmed as a pheno-conversion factor leading from MCI to AD, and clusterin is a promising candidate. Additionally, our meta-analyses revealed APOE as genetic risk factor to convert from a healthy status to MCI [OR = 1.849 (1.587–2.153); P = 2.80  × 10−15] and to a lesser extent from healthy status to SCD [OR = 1.151 (1.015–1.304); P = 0.028]. Thus, we believe that genetic studies in longitudinal SCD and MCI series may provide new therapeutic targets and improve the existing knowledge of AD. This type of studies must be completed on healthy subjects to better understand the natural disease resistance to brain insults and neurodegeneration.

The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have many functions in wounds, including host defence, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound and that the influence of these cells on each stage of repair varies with the specific phenotype. Although the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation or fibrosis under certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of nonhealing and poorly healing wounds. As a result of advances in the understanding of this multifunctional cell, the macrophage continues to be an attractive therapeutic target, both to reduce fibrosis and scarring, and to improve healing of chronic wounds.

The central component of hypoxia sensing in the cell is the hypoxia-inducible factor (HIF) transcriptional complex. HIF activity is deregulated in many human cancers, especially those that are highly hypoxic. Hypoxic tumour cells are usually resistant to radiotherapy and most conventional chemotherapeutic agents, rendering them highly aggressive and metastatic. Overexpression of HIF-α, the regulatory subunit of HIF, is associated with increased vascular density, severity of tumour grade, treatment failure and a poor prognostic outcome with conventional therapies. Therefore HIF is an attractive, although challenging, therapeutic target, and several different strategies have been developed to target HIF directly or indirectly in recent years. This review outlines the preclinical and clinical advances in this arena and discusses which cancers may benefit from HIF-targeted therapy.

Chronic spirochetal infection can cause slowly progressive dementia, cortical atrophy and amyloid deposition in the atrophic form of general paresis. There is a significant association between Alzheimer disease (AD) and various types of spirochete (including the periodontal pathogen Treponemas and Borrelia burgdorferi), and other pathogens such as Chlamydophyla pneumoniae and herpes simplex virus type-1 (HSV-1). Exposure of mammalian neuronal and glial cells and organotypic cultures to spirochetes reproduces the biological and pathological hallmarks of AD. Senile-plaque-like beta amyloid (Aβ) deposits are also observed in mice following inhalation of C. pneumoniae in vivo, and Aβ accumulation and phosphorylation of tau is induced in neurons by HSV-1 in vitro and in vivo. Specific bacterial ligands, and bacterial and viral DNA and RNA all increase the expression of proinflammatory molecules, which activates the innate and adaptive immune systems. Evasion of pathogens from destruction by the host immune reactions leads to persistent infection, chronic inflammation, neuronal destruction and Aβ deposition. Aβ has been shown to be a pore-forming antimicrobial peptide, indicating that Aβ accumulation might be a response to infection. Global attention and action is needed to support this emerging field of research because dementia might be prevented by combined antibiotic, antiviral and anti-inflammatory therapy.

Vitamin B12 (cobalamin, Cbl) is an essential nutrient in human metabolism. Genetic diseases of vitamin B12 utilisation constitute an important fraction of inherited newborn disease. Functionally, B12 is the cofactor for methionine synthase and methylmalonyl CoA mutase. To function as a cofactor, B12 must be metabolised through a complex pathway that modifies its structure and takes it through subcellular compartments of the cell. Through the study of inherited disorders of vitamin B12 utilisation, the genes for eight complementation groups have been identified, leading to the determination of the general structure of vitamin B12 processing and providing methods for carrier testing, prenatal diagnosis and approaches to treatment.