Alternative Splicing and Alzheimer’s Disease

Alzheimer’s disease is a neurodegenerative process whose origin is unknown. It has been associated with this process at least two important proteins: the first is the β-amyloid forming amyloid plaques and the second protein is Tau, which has been determined to precipitates inside the neuron because hyperphosphorylation, causing instability in the axon. Tau microtubule-associated protein (MAP) is essential for the development of neuronal cell polarity. Tau protein is preferentially localized in the axons, whereas MAP2, another neuronal specific microtubule-associated protein, is localized in the somatodendritic domain. Previous studies have demonstrated that the localization of these proteins depends, at least in part, on messenger RNA (mRNA) subcellular localization, that is, Tau mRNA into the axon and MAP2 mRNA into the dendrite. Tau protein has an essential role in the pathology of Alzheimer’s disease, and hyperphosphorylated Tau promotes destabilization of microtubules. Tau alternative splicing generates six isoforms in the adult human brain due to the inclusion or exclusion of exons 2, 3, and 10. The failure in the splicing process of exon 10 generates a tauopathy, which can be carried out by the amyloid peptide; however, the splicing of other exons is less studied. The impact of amyloid peptide on the alternative splicing of exons 2, 3, and 6 caused formed cell processes to retract in differentiated cells and altered the expression of exons 2/3 in cell culture. Expression of exon 6 was repressed under β-amyloid treatment. The molecular mechanism for this amyloid-Tau interaction remains to be determined, but may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer’s disease

Rehabilitating a brain with Alzheimer’s: a proposal

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, originating sporadically in the population aged over 65 years, and advanced age is the principal risk factor leading to AD development. In spite of the large amount of research going on around the globe and all the information now available about AD, there is still no origin or triggering process known so far. Drugs approved for the treatment of AD include tacrine, donepezil, rivastigmine, galantamine, and memantine. These may delay or slow down the degenerative process for a while, but they can neither stop nor reverse its progression. Because that this might be due to a lack of effect of these drugs on degenerating neurons, even when they are able to potentiate the brain in nondegenerative conditions, we propose here an alternative therapy consisting of initial repair of neuronal membranes followed by conventional drug therapies. The rehabilitation of neurons in a degeneration process would enable the drugs to act more effectively on them and improve the effects of treatment in AD patients

Mechanisms of Neuroinflammation

""Mechanisms of Neuroinflammation"" book explains how the neuronal cells become swollen at the moment of the blood-brain barrier disruption and how they lose their immunological isolation. A cascade of cytokines and immune cells from the bloodstream enters the nervous system, inflaming neurons and activating the glia. This produces a neuroinflammatory process that can generate different neurodegenerative diseases. Better understanding of mechanisms that are activated at the time when the damage to the brain occurs could lead to the development of suitable therapies that revert the neuronal inflammation and thus prevent further damage to the nervous system

Neurotherapy for Alzheimer's disease

One of the world's largest pharmaceutical companies apparently will not continue research and development of new drugs against Alzheimer's disease. This situation will leave millions of people in a vulnerable situation. Drugs approved for the treatment of the disease have not been viable and patients always return to the symptoms of the disease. I am of the idea of a primarily pharmacological therapy, using already approved medications that could delay Alzheimer's disease or alleviate some of the symptoms of the disease. This therapy consists of rehabilitating the brain of the person with Alzheimer's, so that later, the drugs, such as acetylcholinesterase inhibitors and memantine act adequately in the neurons, making the treatment indicated by neurologists more effective. This therapy is not expensive and could help the patient to lead a better quality of life. I practically discussed the translational potential of various drugs that have been tested experimentally

Neurons - Dendrites and Axons

The brain is the most complex structure that exists in the universe, consisting of neurons whose function is to receive information through dendrites and transmit information through the axon. In neurosciences one of the main problems that exists are neurodegenerative diseases for which until now there has been no cure. This book is mainly focused on updating the information on the signaling process carried out in the development of axons. Topics such as axon guidance and its interaction with the extracellular matrix are discussed. Other important topics are semaphorins and their relationship with neurodegenerative diseases, and the neurobiology of the gap junction in the dorsal root ganglion. Finally, the topic of bioelectrical interfaces destined to regenerate damaged nerves is covered. The information in this book will be very important both for researchers who work with these issues and doctoral students who are involved in neuroscience

¿Cuál es el mejor modelo de estudio de la enfermedad de Azheimer?

El problema que plantea el estudio de la enfermedad de Alzheimer, aparte de ser una enfermedad multigénica, es que no se tiene un modelo de estudio ya sea in vivo o in vitro que nos permita entender, de manera factible, como es que se inicia la enfermedad. Los modelos hasta ahora propuestos son ratas o ratones transgénicos, sin embargo éstos a lo largo de la vida no presentaran todas las característica de la enfermedad, lo mismo sucede con los cultivos celulares. Es necesario que se acepte y se defina la enfermedad en estos modelo

¿Cuál es el mejor modelo de estudio de la enfermedad de Alzheimer?

A problematic in the study of Alzheimer's disease is the lack of a good model that allows us either in vivo or in vitro to understand how the disease initiates. So far, the proposed models are mainly transgenic mice or rats, however, along their lifetime they do not present all the features of this disease and cell cultures present this same problematic. Thus, we have felt the need to define Alzheimer�s disease in acceptable models able to present all the characteristic events taking place in the pathogenesis of Alzheimer�s that until now we can only observe in postmortem analysis.El problema que plantea el estudio de la enfermedad de Alzheimer, aparte de ser una enfermedad multigénica, es que no se tiene un modelo de estudio ya sea in vivo o in vitro que nos permita entender, de manera factible, como es que se inicia la enfermedad. Los modelos hasta ahora propuestos son ratas o ratones transgénicos, sin embargo éstos a lo largo de la vida no presentaran todas las característica de la enfermedad, lo mismo sucede con los cultivos celulares. Es necesario que se acepte y se defina la enfermedad en estos modelos y que cumplan con las características que hasta ahora solo ofrecen los estudios post-mortem

Post-accidente vascular cerebral: Hacia una terapia global

El accidente vascular cerebral es el padecimiento neurológico, más frecuente, que puede llevar a la incapacidad funcional de una persona. El tratamiento primario por lo general no va seguido de una terapia global para inhibir el proceso neuroinflamatorio. Es indispensable que se inhiba el proceso neuroinflamatorio para que la persona pueda si es posible continuar con su vida normal. Inhibir la expresión de la ciclooxigenasa 2 (COX-2) permitirá que el paciente se recupere debidamente. Nosotros proponemos una terapia global a base de medicamentos como la nimesulida y el citalopram y complementos como los ácidos omega-3 y el resveratrol, que hará que el paciente se recupere de manera satisfactoria. Presentamos un caso severo de una persona que sufrió primero un derrame cerebral y después un trauma craneal y que accedió a seguir esta terapi