Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis

Abstract Protein aggregation is common to dozens of diseases including prionoses, diabetes, Parkinson’s and Alzheimer’s. Over the past 15 years, there has been a paradigm shift in understanding the structural basis for these proteinopathies. Precedent for this shift has come from investigation of soluble Aβ oligomers (AβOs), toxins now widely regarded as instigating neuron damage leading to Alzheimer’s dementia. Toxic AβOs accumulate in AD brain and constitute long-lived alternatives to the disease-defining Aβ fibrils deposited in amyloid plaques. Key experiments using fibril-free AβO solutions demonstrated that while Aβ is essential for memory loss, the fibrillar Aβ in amyloid deposits is not the agent. The AD-like cellular pathologies induced by AβOs suggest their impact provides a unifying mechanism for AD pathogenesis, explaining why early stage disease is specific for memory and accounting for major facets of AD neuropathology. Alternative ideas for triggering mechanisms are being actively investigated. Some research favors insertion of AβOs into membrane, while other evidence supports ligand-like accumulation at particular synapses. Over a dozen candidate toxin receptors have been proposed. AβO binding triggers a redistribution of critical synaptic proteins and induces hyperactivity in metabotropic and ionotropic glutamate receptors. This leads to Ca2+ overload and instigates major facets ...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

Related Links:

CONCLUSIONS Ministry of Health policies on the amount of patient cost sharing and on the choice of medicines on coverage lists have substantial impacts on overall generic sales volume in retail pharmacies.
Source: Revista de Saude Publica - Category: International Medicine & Public Health Source Type: research
es EL Abstract Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week p...
Source: Braz J Med Biol Res - Category: Research Authors: Tags: Braz J Med Biol Res Source Type: research
This study was conducted to enhance the rate of advance care planning conversations and documentation by improving knowledge, attitudes, and skills of caregivers.      Read more   Violence and Trauma ...
Source: Johns Hopkins University and Health Systems Archive - Category: Nursing Source Type: news
Source: BMJ News - Category: General Medicine Source Type: research
Publication date: Available online 16 October 2019Source: Pharmacology &TherapeuticsAuthor(s): Kazu Nakazawa, Kiran SapkotaAbstractN-methyl-D-aspartate (NMDA) receptor (NMDAR) hypofunction plays a key role in pathophysiology of schizophrenia. Since NMDAR hypofunction has also been reported in autism, Alzheimer’s disease and cognitive dementia, it is crucial to identify the location, timing, and mechanism of NMDAR hypofunction for schizophrenia for better understanding of disease etiology and for novel therapeutic intervention. In this review, we first discuss the shared underlying mechanisms of NMDAR hypofunction...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
Abstract Galanthamine is an Amaryllidaceae-derived acetylcholinesterase inhibitor used to treat memory impairment in Alzheimer's disease and vascular dementia. There is evidence that galanthamine, in addition to its effects on acetylcholinesterase, may enhance or inhibit brain nicotinic acetylcholine receptors, which could increase or decrease the therapeutic efficacy of galanthamine, respectively. Here, we evaluated the effects of galanthamine and two others Amaryllidaceae acetylcholinesterase inhibitors (haemanthamine and tazettine) analyzed by gas chromatography – mass spectrometry and identified by comparing thei...
Source: Revista Brasileira de Farmacognosia - Category: Drugs & Pharmacology Source Type: research
Abstract The species Kalanchoe laciniata (L.) DC. and Bryophyllum pinnatum (Lam) Pers. are native from Brazil and Madagascar, respectively. Both belonging to the Crassulaceae family and being widely used by population as a natural anti-inflammatory agent. These species have similar leaf morphology and for this reason, they are known by the same popular name as “ sai ão ” or “ coirama ” . Several studies have been published involving different parts and preparations of these species. Therefore, this review aims to provide an update overview about the traditional uses, chemical constitution, ph...
Source: Revista Brasileira de Farmacognosia - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 16 October 2019Source: Anaesthesia Critical Care &Pain MedicineAuthor(s): M.S. Raghuraman, A. Arthi, M.S. Iswaryarajan Hercule
Source: Anaesthesia, Critical Care and Pain Medicine - Category: Anesthesiology Source Type: research
ConclusionThis study showed that calcitonin could be helpful analgesic agent in different painful situations. Calcitonin can be considered an eligible treatment for acute pains related to vertebral fractures and a feasible alternative for the treatment of the acute and chronic neuropathic pains where other medications might fail.ResumoJustificativa e objetivosA calcitonina é um hormônio polipeptídico que regula o metabolismo do cálcio no organismo. Por muitos anos a calcitonina tem sido usada para manter e melhorar a densidade mineral óssea e reduzir a incidência de fraturas. Muitos ...
Source: Brazilian Journal of Anesthesiology - Category: Anesthesiology Source Type: research
People at high risk for serious flu complications are those with conditions such as asthma, chronic lung disease, diabetes, heart disease, morbid obesity, or adults aged 65 years or older.FDA Approvals
Source: Medscape Allergy Headlines - Category: Allergy & Immunology Tags: Infectious Diseases News Alert Source Type: news
More News: Amnesia | Brain | Dementia | Diabetes | Endocrinology | Hyperactivity | Insulin | Neurology | Study | Toxicology