Abstract: Developing effective therapies for serious neurological insults remains a major challenge for biomedical research. Despite intense efforts, the ability to promote functional recovery after contusion injuries, ischemic insults, or the onset of neurodegenerative diseases in the brain and spinal cord remains very limited even while the need for such therapies is increasing with an aging population. Recent studies suggest that cellular therapies utilizing mesenchymal stem cells (MSCs) may provide a functional benefit in a wide range of neurological insults. MSCs derived from a variety of tissue sources have been therapeutically evaluated in animal models of stroke, spinal cord injury, and multiple sclerosis. In each situation, treatment with MSCs results in substantial functional benefit and these pre-clinical studies have led to the initiation of a number of clinical trials worldwide in neural repair. ... Read more

Abstract: Given improvements in viral vector design, production and efficiency of transduction in the central nervous system (CNS), as well as increased knowledge of neuropathological mechanisms in neurological disorders, success in treating a CNS disorder with gene transfer seems inevitable. Several different vector systems have been studied extensively and the adeno-associated viral vector system has been utilized in most early stage clinical trials in neurological disorders. Other vector systems, such as lentivirus, adenovirus, and herpes simplex virus are also viable vector platforms that should fill significant clinical niches based on their specific characteristics. In addition to the choice of the appropriate vector, the proper choice of transgene for the appropriate strategy to treat a neurological disorder is also critical. The example of glial cell line-derived neurotrophic factor ligands to treat Parkinson's disease is used to illustrate the importance of the interface between interpretation of pre-clinical data and consideration of the natural history of the disorder. This interface dictates the proper design of clinical trials that are capable of testing whether the treatment is actually successful. ... Read more

Abstract: Increasing evidence suggests an important role for programmed cell death (PCD) pathways in aging phenotypes across species. PCD is critical to the homeostasis of tissues maintained by cell division, for example, the blood and the lining of the gut. During aging, accumulated cellular damage and non-optimal systemic signaling can cause too little cell death (hyperproliferation and cancer), or too much cell death (tissue atrophy and ectopic cell death), thereby limiting tissue function and life span. For these reasons PCD pathways are promising targets for interventions in aging and aging-related diseases: reactivation of PCD may be beneficial in clearing cancerous and senescent cells, whereas inhibiting PCD may help prevent muscle atrophy and nervous system degeneration. ... Read more

Abstract: Ghrelin is a recently identified gastric hormone that displays strong growth hormone (GH) releasing activity mediated by the GH secretagogue receptor (GHS-R). While this unique endogenous peptide participates in the regulation of energy homeostasis, increases food intake, and decreases energy expenditure, its ability to modulate immune regulation is another important feature. Here we discuss the effect of ghrelin on the immune system. Ghrelin was initially reported as an immune enhancing factor. More recently, however, the immunosuppressive effects of ghrelin have been found in several animal models including bowel disease, arthritis, and sepsis and endotoxemia. We recently demonstrated that exogenous administration of ghrelin suppressed experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis in association with the reduction of pro-inflammatory cytokines in microglia. These results shed light on the new role of ghrelin in the regulation of disorders that pro-inflammatory cytokines contribute to the pathogenesis such as neuroinflammatory and mental diseases. ... Read more

Abstract: The APOE ε4 allele is associated with risk of late-onset Alzheimer's disease (AD). Longitudinal memory decline in asymptomatic APOE ε4 carriers shows greater acceleration compared with non-carriers, with a possible allele-dose effect, and begins prior to age 60. These results correlate with imaging and neuropathological studies that show AD-like changes at this age and collectively support the existence of a presymptomatic stage of AD. ... Read more

Abstract: The process of refolding or degrading misfolded proteins is the most important function of protein quality control (PQC) system. An imbalance between the capacity of PQC system and the quantity and severity of misfolded proteins may result in protein aggregate accumulation, which can ultimately contribute to a class of diseases referred to as conformational disorders. Numerous lines of evidence suggest that Ubiquilin 1 is an important component in PQC. Ubiquilin 1 has been indicated to be involved in the pathophysiology of neurodegenerative diseases and cancer. Here we review the evidence that Ubiquilin 1 is an important component of the PQC system and also review the role of Ubiquilin 1 in human diseases. ... Read more

Abstract: Neurodegenerative diseases, such as Huntington's disease, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS), are progressive neurological diseases that affect millions of people worldwide. Recent identification and advances in our understanding of multi-potent neural stem cells/progenitors in the mature CNS has raised the possibility that these discoveries can be translated into an effective therapy for degenerative neurological disease. ... Read more

Abstract: As with many other molecular agents that are involved in multiple aspects of cellular processes, E2F1 plays a dual role of cellular proliferation and apoptosis. How to take advantage of the apoptosis induction and sensitization properties of E2F1 for therapeutic purposes while minimizing its other properties has a significant bearing on how to turn a functionally complex molecule such as E2F1 into a drug target. ... Read more

Abstract: In addition to the immune system, apoptosis plays a role in the nervous system. An excessive number of cells are generated during embryogenesis and only neurons that make the correct connections at the right time survive. But then, these surviving neurons do not divide and they need to make it through the entire life of the organism and cannot be replaced once they are dead. The control over death and survival is therefore vitally important. ... Read more

Abstract: There are 4 kinds of memories. The authors describe here how recalling what you had for dinner last night, recalling factual knowledge such as the color of a lion, pressing the home phone number on the keypad without conscious effort, keeping a phone number in mind are governed by episodic, semantic, procedural and working memory, respectively. ... Read more