Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases.
ABSTRACT Brain mononuclear phagocytes (MP, bone marrow monocyte-derived macrophages, perivascular macrophages, and microglia) function to protect the nervous system by acting as debris scavengers, killers of microbial pathogens, and regulators of immune responses. MP are activated by a variety of environmental cues and such inflammatory responses elicit cell injury and death in the nervous system. MP immunoregulatory responses include secretion of neurotoxic factors, mobilization of adaptive immunity, and cell chemotaxis. This incites tissue remodelling and blood-brain barrier dysfunction. As disease progresses, MP secretions engage neighboring cells in a vicious cycle of autocrine and paracrine amplification of inflammation leading to tissue injury and ultimately destruction. Such pathogenic processes tilt the balance between the relative production of neurotrophic and neurotoxic factors and to disease progression. The ultimate effects that brain MP play in disease revolves "principally" around their roles in neurodegeneration. Importantly, common functions of brain MP in neuroimmunity link highly divergent diseases (for example, human immunodeficiency virus type-one associated dementia, Alzheimer's disease and Parkinson's disease). Research into this process from our own laboratories and those of others seek to harness MP inflammatory processes with the intent of developing therapeutic interventions that block neurodegenerative processes and improve the quality of life in affected people.
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ABSTRACT: A commercially available sample of poly(α-D)galacturonic acid, i.e. pectic acid, was characterized according to the size and shape of its molecule through the volumetric and transport properties of its aqueous solutions. Thus, the average molecular weight of polygalacturonic acid and its average degree of polymerization were estimated on the basis of viscosity measurements. The length-to-diameter ratio, calculated by means of Simha's equation, strengthened the assumption that pectic acid is a fairly rigid, rod-like molecule. By potentiometric titration of aqueous solutions of poly(α-D)galacturonic acid with several alkaline and tetraalkylammonium hydroxides, the effects of the size and nature of the counterion on the degree and extent of dissociation of the polymeric acid were estimated. In evaluation of the potentiometric curves the treatment proposed by Mandel for weak polyacids not exhibiting a conformational transition during titration was used. In addition, the nonelectrostatic character of polyion-counterion interactions was confirmed by the application of the cell model to the polyelectrolytic solute investigated.
Article: Microglial pathology[Show abstract] [Hide abstract]
ABSTRACT: This paper summarizes pathological changes that affect microglial cells in the human brain during aging and in aging-related neurodegenerative diseases, primarily Alzheimer¿s disease (AD). It also provides examples of microglial changes that have been observed in laboratory animals during aging and in some experimentally induced lesions and disease models. Dissimilarities and similarities between humans and rodents are discussed in an attempt to generate a current understanding of microglial pathology and its significance during aging and in the pathogenesis of Alzheimer dementia (AD). The identification of dystrophic (senescent) microglia has created an ostensible conflict with prior work claiming a role for activated microglia and neuroinflammation during normal aging and in AD, and this has raised a basic question: does the brain¿s immune system become hyperactive (inflamed) or does it become weakened (senescent) in elderly and demented people, and what is the impact on neuronal function and cognition? Here we strive to reconcile these seemingly contradictory notions by arguing that both low-grade neuroinflammation and microglial senescence are the result of aging-associated free radical injury. Both processes are damaging for microglia as they synergistically exhaust this essential cell population to the point where the brain¿s immune system is effete and unable to support neuronal function.09/2014; 2(1):142. DOI:10.1186/PREACCEPT-1035265697142235