Factors associated with time to disability progression in patients with multiple sclerosis.

Objectives.: Motivation for the study: multiple sclerosis (MS) is a complex disease that requires management by different disciplines. Data on Latin American patients is scarce, therefore, the usually used theoretical references are from other population groups.

Neurodegeneration and convergent factors contributing to the deterioration of the cytoskeleton in Alzheimer's disease, cerebral ischemia and multiple sclerosis (Review).

The cytoskeleton is the main intracellular structure that determines the morphology of neurons and maintains their integrity. Therefore, disruption of its structure and function may underlie several neurodegenerative diseases. This review summarizes the current literature on the tau protein, microtubule-associated protein 2 (MAP2) and neurofilaments as common denominators in pathological conditions such as Alzheimer's disease (AD), cerebral ischemia, and multiple sclerosis (MS).

β-Secretase 1's Targeting Reduces Hyperphosphorilated Tau, Implying Autophagy Actors in 3xTg-AD Mice.

β-site APP cleaving enzyme 1 (BACE1) initiates APP cleavage, which has been reported to be an inducer of tau pathology by altering proteasome functions in Alzheimer's disease (AD). However, the exact relationship between BACE1 and PHF (Paired Helical Filaments) formation is not clear. In this study, we confirm that BACE1 and Hsc70 are upregulated in the brains of AD patients, and we demonstrate that both proteins show enhanced expression in lipid rafts from AD-affected triple transgenic mouse brains.

Cyclin-Dependent kinase 5 targeting prevents β-Amyloid aggregation involving glycogen synthase kinase 3β and phosphatases.

Inappropriate activation of cyclin-dependent kinase 5 (CDK5) resulting from proteolytic release of the activator fragment p25 from the membrane contributes to the formation of neurofibrillary tangles, β-amyloid (βA) aggregation, and chronic neurodegeneration. At 18 months of age, 3× Tg-AD mice were sacrificed after either 3 weeks (short term) or 1 year (long term) of CDK5 knockdown. In short-term-treated animals, CDK5 knockdown reversed βA aggregation in the hippocampi via inhibitory phosphorylation of glycogen synthase kinase 3β Ser9 and activation of phosphatase PP2A.

ROCK inhibition prevents tau hyperphosphorylation and p25/CDK5 increase after global cerebral ischemia.

Rho-kinase (ROCK) is a downstream effector of RhoA, which has been associated with growth cone collapse and retraction in neurons. ROCK inhibition has been shown to protect against ischemic damage, thereby improving short-term collateral flow, inhibiting platelet aggregation, leukocyte adhesion, and preventing neuronal death. However, little is known about the long-term effects of ROCK inhibition on behavior and neuroprotection.

Silencing of CDK5 as potential therapy for Alzheimer's disease.

Neurodegeneration is one of the greatest public health challenges for the 21st century. Among neurodegenerative diseases, Alzheimer's disease (AD) is the most prevalent and best characterized. Nevertheless, despite the large investment in AD research, currently there is no effective therapeutic option.

Rac1 activity changes are associated with neuronal pathology and spatial memory long-term recovery after global cerebral ischemia.

Excitotoxicity is the main event during neurological disorders producing drastic morphological and functional changes. Rac-GTPase is involved in cytoskeletal remodeling and survival. However, the role of Rac1 after cerebral ischemia has not been completely understood yet.