Cross Currents in Protein Misfolding Disorders: Interactions and Therapy

Morales, Rodrigo; Green, Kristi M.; Soto, Claudio

doi:10.2174/187152709789541998

Cited by 67 publications

(47 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After acute traumatic injury in animal models, TDP-43 expression is upregulated and TDP-43 relocates from the neuronal nucleus to accumulate in the neuronal cytoplasm [134, 135] TDP-43 binds to many cellular transcripts including tau and alpha synuclein, and its dysregulation may underlie some of the pathologies seen with these proteins [162]. In particular, TDP-43 may influence tau iso-form expression [136]. There is also evidence that alteration in tau protein metabolism including hyperphosphorylation, tau phosphatase resistance, and deposition of PHF-tau intracellular aggregates may be found in diseases characterized by abnormal TDP-43 metabolism, such as ALS [177].…”

Section: Adverse Neuropathological Outcomes Associated With Sports Pamentioning

confidence: 99%

The neuropathology of sport

et al. 2013

View full text Add to dashboard Cite

The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable. Physical activity reduces the risk for cardiovascular disease, type 2 diabetes, hypertension, obesity, and stroke, and produces beneficial effects on cholesterol levels, antioxidant systems, inflammation, and vascular function. Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration. Nonetheless, the play of sports is associated with risks, including a risk for mild TBI (mTBI) and, rarely, catastrophic traumatic injury and death. There is also growing awareness that repetitive mTBIs, such as concussion and subconcussion, can occasionally produce persistent cognitive, behavioral, and psychiatric problems as well as lead to the development of a neurodegeneration, chronic traumatic encephalopathy (CTE). In this review, we summarize the beneficial aspects of sports participation on psychological, emotional, physical and cognitive health, and specifically analyze some of the less common adverse neuropathological outcomes, including concussion, second-impact syndrome, juvenile head trauma syndrome, catastrophic sudden death, and CTE. CTE is a latent neurodegeneration clinically associated with behavioral changes, executive dysfunction and cognitive impairments, and pathologically characterized by frontal and temporal lobe atrophy, neuronal and axonal loss, and abnormal deposits of paired helical filament (PHF)-tau and 43 kDa TAR deoxyribonucleic acid (DNA)-binding protein (TDP-43). CTE often occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including motor neuron disease (CTE-MND). Although the incidence and prevalence of CTE are not known, CTE has been reported most frequently in American football players and boxers. Other sports associated with CTE include ice hockey, professional wrestling, soccer, rugby, and baseball.

show abstract

Section: Adverse Neuropathological Outcomes Associated With Sports Pamentioning

confidence: 99%

The neuropathology of sport

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In addition to the progressive death of neurons, neurodegenerative diseases cause accumulation of aberrantly-folded “key” disease proteins (Morales and Green, 2009; Aguzzi and O'Connor, 2010; Perry et al, 2012), which individually characterize each of these conditions, including amyloid β in Alzheimer's disease (AD), α synuclein in Parkinson's disease (PD) and prion protein (PrP Sc ) in prion diseases such as Creutzfeldt-Jakob disease (CJD) (Prusiner, 1982; Olanow and Prusiner, 2009). These aggregates are considered hallmarks of neurodegenerative diseases (Ashe and Aguzzi, 2013; Prusiner, 2013).…”

Section: Introductionmentioning

confidence: 99%

Chronic Progressive Neurodegeneration in a Transgenic Mouse Model of Prion Disease

et al. 2016

View full text Add to dashboard Cite

Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic proteins without an accompanying neurodegeneration pattern. The lack of a comprehensive model hinders efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice mimicking for genetic Creutzfeldt-Jacob disease as compared to age-matched wild-type mice. Mice exhibited a neurodegenerative process of progressive reduction in cortical neurons and synapses starting at age of 4–6 months, in accord with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with neurological disease progression, indicating these mice can serve as a model for neurodegenerative diseases.

show abstract

“…This study has demonstrated that the seeding potency of homologous AA fibrils is higher than that of heterologous fibrils. Homologous seeding has been documented for most proteins implicated in misfolding diseases [16,17]. In this study, peak AA deposition was observed 20 days after AA fibril administration.…”

Section: Discussionmentioning

confidence: 56%