Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of lithium carbonate for the treatment of bipolar disorder in older adults is decreasing at a significant rate. This change in prescription pattern is occurring at a time when all evidence-based treatment guidelines and systematic reviews still recommend lithium as a first-line treatment for bipolar disorder. Despite having the strongest evidence base for effectiveness, lithium does pose significant concerns in the older population, including the risk of drug interactions that cause toxicity associated with decreased creatinine clearance. The evidence for lithium's impact on chronic renal disease is still controversial and is reviewed in this article. Mixed evidence exists regarding the impact of lithium on suicide risk, although there is a consensus that it does have protective properties through its mood-stabilizing effect. Because of the very limited research base regarding the use of lithium in old age, guidelines for dosing and maintenance of serum concentrations are not well established, and this may be leading to increased episodes of lithium toxicity. At the same time that these legitimate concerns about lithium are being highlighted, evidence has accumulated that suggests that lithium may have neuroprotective properties. Its action of inhibiting the enzyme glycogen synthase kinase-3 may be responsible in part for a decrease in the induction of amyloid beta peptide and hyperphosphorylated tau protein, which have been implicated in the development of Alzheimer's disease. Very little evidence supports use of alternatives to lithium such as other mood-stabilizing agents, including atypical antipsychotics, in older adults. Thus, before we abandon lithium as a first-line agent, we should ensure that the guidelines for lithium treatment are safe, practical and effective. Newer agents must be appropriately tested in older adults before replacing this longstanding first-line treatment for bipolar disorder.
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PMID:Lithium for older adults with bipolar disorder: Should it still be considered a first-line agent? 2065 89

Over the past decade, athletic-related chronic traumatic encephalopathy (CTE) has garnered a great deal of attention in the popular press and, more recently, in the scientific press. With increasing frequency, sports medicine practitioners and providers are faced with questions from the parents of high school football players about CTE and the risk posed to children who participate in this or other contact or collision sports. The purpose of this review was to summarize the research on CTE in an attempt to provide some evidence-based answers to frequently asked questions in clinics from parents. Addressed are (1) the definitions of CTE and its symptoms, (2) the evidence for CTE in football, (3) abnormal tau protein, (4) the use of neuroimaging in CTE diagnosis, (5) risk for CTE, (6) CTE diagnosis in youth, (7) CTE and its relationship to suicide, and (8) contact and collision sports as a risk factor for permanent brain injury or death.
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PMID:Talking with parents of high school football players about chronic traumatic encephalopathy: a concise summary. 2490 88

Traumatic brain injury (TBI) is a leading cause of death and disability, contributing to ~30% of all injury-related deaths in the US. TBI occurs when a force transmitted to the head causes neuropathologic damage and impairment of brain function. TBI doubles risk of suicide and is the major determinant of acquired seizure disorders. TBI arising from closed head trauma (CHT) significantly increases the risk of developing Alzheimer's disease (AD), Parkinson's disease (PD) and chronic traumatic encephalopathy (CTE). Evidence for a possible role of TBI as a risk factor for sporadic amyotrophic lateral sclerosis (sALS) has been provided by studies of professional players of European football. Depending on age, genetic make-up (in particular, being a carrier of one or two ApoE4 alleles), the number of TBIs sustained, their severity, the time periods involved, and many other factors that affect vulnerability, decades may pass after occurrence of one or more TBIs before sequelae such as AD, PD, sALS or CTE become clinically evident. Among college and professional football players who experience repeated concussions and sub-concussive blows to the head, the risk of developing CTE increases with the number of years actively devoted to the sport, and the degree of exposure to physical impacts inherent in the position played. Following a moderate or severe concussion, or a series of mild blows to the head, the brain may undergo subtle pathophysiological changes that are unlikely to be detected with confidence using available diagnostic methods. Biomarkers are being sought that can help the attending physician infer the likely presence of an ongoing occult neurodegenerative process. One example of the adverse effect of collision on the brain is "heading" the soccer ball-a feat that, repeated over years of competition, has been found to produce severe brain damage in veteran players. CTE has attracted increasing national attention because of its devastating effects in a high proportion of retired professional players of American football. In a study of brains from deceased former football players, contributed mostly by family members, CTE was neuropathologically diagnosed in 110 of 111 of National Football League (NFL) veterans. In the CTE-positive subjects, the authors observed extensive brain atrophy, astrogliosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. CTE's neuropathology has been formally defined as a tauopathy characterized by a distinct perivascular accumulation of hyperphosphorylated tau in neurons and astrocytes within cerebral sulci. Although the mechanism that underlies the unforeseen emergence of CTE long after the occurrence of one or more closed head traumas is unknown, an explanation proposed by Albayram and associates is persuasive. They discovered TBI-induced neuronal production of the toxic compound cis P-tau, an abnormal and destructive isomer of the normal and benign trans P-tau, in mouse models of CTE. Cis P-tau produced a CTE-like syndrome via a process they termed cistauosis. Cistauosis can be blocked in laboratory animals by cis P-tau monoclonal antibody, which prevents later development of tau tangles, brain atrophy and virtual CTE. In a subsequent study, the same group found in human samples obtained post-TBI from a variety of causes, that cis P-tau is induced in cortical axons and cerebrospinal fluid and positively correlates with axonal injury and clinical outcome. Thus, cis P-tau appears to contribute to short-term and long-term sequelae after TBI, but may be subject to neutralization by cis-antibody treatment.
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PMID:Traumatic brain injury (TBI) in collision sports: Possible mechanisms of transformation into chronic traumatic encephalopathy (CTE). 3161 Aug 56