NeuroImmunology

Abstract

Alzheimer's disease (AD) is the world's most common dementing illness, affecting over 150 million patients. Classically AD has been viewed as a neurodegenerative disease of the elderly, characterized by the extracellular deposition of misfolded amyloid-β (Aβ) peptide and the intracellular formation of neurofibrillary tangles. Only recently has neuroinflammation emerged as an important component of AD pathology. Experimental, genetic and epidemiological data now indicate a crucial role for activation of the innate immune system as a disease-promoting factor. The sustained formation and deposition of Aβ aggregates causes chronic activation of the immune system and disturbance of microglial clearance functions. Here we review advances in the molecular understanding of the inflammatory response in AD that point to novel therapeutic approaches for the treatment of this devastating disease.

Via Krishan Maggon

Abstract

Alzheimer's disease (AD) is devastating and leads to permanent losses of memory and other cognitive functions. Although recent genetic evidences strongly argue for a causative role of Aβ in AD onset and progression (Jonsson et al., 2012), its role in AD etiology remains a matter of debate. However, even if not the sole culprit or pathological trigger, genetic and anatomical evidences in conjunction with numerous pharmacological studies, suggest that Aβ peptides, at least contribute to the disease. How Aβ contributes to memory loss remains largely unknown. Soluble Aβ species referred to as Aβ oligomers have been shown to be neurotoxic and induce network failure and cognitive deficits in animal models of the disease. In recent years, several proteins were described as potential Aβ oligomers receptors, amongst which are the receptor tyrosine kinases of Eph family. These receptors together with their natural ligands referred to as ephrins have been involved in a plethora of physiological and pathological processes, including embryonic neurogenesis, learning and memory, diabetes, cancers and anxiety. Here we review recent discoveries on Eph receptors-mediated protection against Aβ oligomers neurotoxicity as well as their potential as therapeutic targets in AD pathogenesis.

  

Via Krishan Maggon