ABSTRACT
Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.
Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Humans , Alzheimer Disease/pathology , Calcium/metabolism , Amyloid beta-Peptides/metabolism , Calcium, Dietary , Calcium Channels, L-TypeABSTRACT
Alzheimer's disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate in several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress and lipid metabolism (along with a critical role in apolipoprotein E function). Current evidence shows that astrocytes have both neuroprotective and neurotoxic effects depending on the disease stage and microenvironmental factors. Furthermore, astrocytes appear to be affected by the presence of amyloid-beta (Aß), with alterations in calcium levels, gliotransmission and proinflammatory activity via RAGE-NF-κB pathway. In addition, astrocytes play an important role in the metabolism of tau and clearance of Aß through the glymphatic system. In this review, we will discuss novel pharmacological and non-pharmacological treatments focused on astrocytes as therapeutic targets for AD. These interventions include effects on anti-inflammatory/antioxidant systems, glutamate activity, lipid metabolism, neurovascular coupling and glymphatic system, calcium dysregulation, and in the release of peptides which affects glial and neuronal function. According to the AD stage, these therapies may be of benefit in either preventing or delaying the progression of the disease.
Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Astrocytes/metabolism , Calcium/metabolism , Amyloid beta-Peptides/metabolism , Neurons/metabolismABSTRACT
RESUMEN Raoultella Planticola es una bacteria que se ha descrito recientemente en la literatura como patógeno emergente de infecciones urinarias, abdominales y pulmonares. A continuación, se presenta el caso de un paciente de 63 años con antecedente de sobrepeso y dislipidemia hospitalizado en contexto de neumonía por SARS CoV2 quien presenta sobreinfección por R. Planticola y E. Aerogenes. Recibió manejo con Cefepime por 7 días con adecuada evolución clínica.
ABSTRACT Raoultella planticola is a bacterium that has been recently described in the literature as an emerging pathogen that causes urinary, abdominal, and lung infections. We present the case of a 63-year-old overweight and with dyslipidemia that was hospitalized because of a SARS-CoV-2 infection. He developed R. planticola and E. aerogenes superinfections. He was treated with cefepime for seven days, and he recovered uneventfully.
