A new hope: Mitochondria, a critical factor in the war against prions.

Prion diseases encompass a group of incurable neurodegenerative disorders that occur due to the misfolding and aggregation of infectious proteins. The most well-known prion diseases are Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (also known as mad cow disease), and kuru. It is estimated that around 1-2 persons per million worldwide are affected annually by prion disorders. Infectious prion proteins propagate in the brain, clustering in the cells and rapidly inducing tissue degeneration and death. Prion disease alters cell metabolism and energy production damaging mitochondrial function and dynamics leading to a fast accumulation of damage. Dysfunction of mitochondria could be considered as an early precursor and central element in the pathogenesis of prion diseases such as in sporadic CJD. Preserving mitochondria function may help to resist the rapid spread and damage of prion proteins and even clearance. In the war against prions and other degenerative diseases, studying how to preserve the function of mitochondria by using antioxidants and even replacing them with artificial mitochondrial transfer/transplant (AMT/T) may bring a new hope and lead to an increase in patients' survival. In this perspective review, we provide key insights about the relationship between the progression of prion disease and mitochondria, in which understanding how protecting mitochondria function and viability by using antioxidants or AMT/T may help to develop novel therapeutic interventions.

The war against Alzheimer, the mitochondrion strikes back!

Alzheimer's disease (AD) is a leading neurodegenerative pathology associated with aging worldwide. It is estimated that AD prevalence will increase from 5.8 million people today to 13.8 million by 2050 in the United States alone. AD effects in the brain are well known; however, there is still a lack of knowledge about the cellular mechanisms behind the origin of AD. It is known that AD induces cellular stress affecting the energy metabolism in brain cells. During the pathophysiological advancement of AD, damaged mitochondria enter a vicious cycle, producing reactive oxygen species (ROS), harming mitochondrial DNA and proteins, leading to more ROS and cellular death. Additionally, mitochondria are interconnected with the plaques formed by amyloid-ß in AD and have underlying roles in the progression of the disease and severity. For years, the biomedical field struggled to develop new therapeutic options for AD without a significant advancement. However, mitochondria are striking back existing outside cells in a new mechanism of intercellular communication. Extracellular mitochondria are exchanged from healthy to damaged cells to rescue those with a perturbed metabolism in a process that could be applied as a new therapeutic option to repair those brain cells affected by AD. In this review we highlight key aspects of mitochondria's role in CNS' physiology and neurodegenerative disorders, focusing on AD. We also suggest how mitochondria strikes back as a therapeutic target and as a potential agent to be transplanted to repair neurons affected by AD.

Fighting Parkinson's disease: The return of the mitochondria.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, worldwide. PD neuro-energetically affects the extrapyramidal system, by the progressive loss of striatal dopaminergic neurons in the substantia nigra pars compacta, leading to motor impairment. During the progression of PD, there will be an increase in mitochondrial dysfunction, reactive oxygen species (ROS), stress and accumulation of α-synuclein in neurons. This results in mitochondrial mutations altering their function and fission-fusion mechanisms and central nervous system (CNS) degeneration. Intracellular mitochondrial dysfunction has been studied for a long time in PD due to the decline of mitochondrial dynamics inside neurons. Mitochondrial damage-associated molecular patterns (DAMPs) have been known to contribute to several CNS pathologies especially PD pathogenesis. New and exciting evidence regarding the exchange of mitochondria between healthy to damaged cells in the central nervous system (CNS) and the therapeutic use of the artificial mitochondrial transfer/transplant (AMT) marked a return of this organelle to develop innovative therapeutic procedures for PD. The focus of this review aims to shed light on the role of mitochondria, both intra and extracellularly in PD, and how AMT could be used to generate new potential therapies in the fight against PD. Moreover, we suggest that mitochondrial therapy could work as a preventative measure, motivating the field to move towards this goal.

Epilepsia mioclonica de la adolescencia: un estudio de 39 pacientes

Teinta e nueve pacientes fueron diagnosticados de epilepsia mioclónica de la adolescencia, de un grupo de 65 pacientes con epilepsias y síndromes epilépticos generalizados, constituyendo el 60% de éstos. Ninguno de los pacientes había sido diagnosticado como portador de este síndrome y el promdedio de años desde el inicio de la enfermedad hasta el diagnóstico fue de 7 años. El Promedio de edad de inciio fue de 14 años, con una variación de 8 a 22 años. En 56% de los pacientes se presentó el síndrome con ausencias, mioclonías y crisis clónico-tónico-clónicas generalizadas. El 31% de los pacientes tuvieron antecedentes de epilespia en sus padres o hermanos. Se analizaron los hallazgos electroencefalográficos, los factores desencadenantes de crisis y la respuesta terapéutica. La epilepsia miclónica de la adolescencia de Janz ha constituído el 15% de todos los pacientes con crisis epilépticas que han acudido a un servicio de neurología de un hospital general por lo que reconocerlo es indispensable para el manejo adecuado de la epilelpsia