功能障碍内质网（ER）和线粒体（MT）在阿尔茨海默氏病：对ER-MT串扰的作用

Title:Dysfunction of Endoplasmic Reticulum (ER) and Mitochondria (MT) in Alzheimer's Disease: The Role of the ER-MT Cross-Talk

Volume: 12 Issue: 7

Author(s): Katalin Volgyi, Gábor Juhász, Zsolt Kovacs and Botond Penke

Affiliation:

关键词: β淀粉样蛋白，内质网，线粒体相关内质网膜，线粒体故障，突触线粒体，折叠蛋白应答。

摘要: A common feature of neurodegenerative diseases is the formation of misfolded, mostly enzyme resistant proteins. These substances may form toxic assemblies according to the current concept of the neurodegenerative diseases. Overlapping of the misfolded proteins is typical in these disorders. The formation of misfolded proteins and toxic aggregates point to a common pathway of these disorders: failure in normal protein folding in the ER as a consequence of ER-stress and mitochondrial energy production. Alzheimer's disease (AD) is a rather heterogeneous, multifactorial disorder with wide clinical heterogeneity and is classified into several subtypes. In AD the processing of the amyloid precursor protein (APP) and formation of toxic β-amyloid (Aβ) structures occur intraneuronally. Aβ affects both ER and mitochondria and disturbs Ca²⁺-homeostasis of the cells. Mitochondrial dysfunction is one of the main pathological events in AD. Mitochondria accumulate Aβ derived from the ER/Golgi or from the mitochondriaassociated ER-membranes (MAM). Free radicals, oxidative stress and increasing Ca²⁺-concentration in mitochondria cause decreased ATP production. Mitochondrial dynamic and trafficking are also altered as a result of Aβ toxicity. Synaptic mitochondria show a very high vulnerability. Depletion of Ca²⁺ level in the ER results in dysfunction of protein folding and evokes unfolded protein response (UPR), and affects also mitochondria. MAM may play special role in the ERmitochondria cross talk. Mitochondria themselves (using mitochondria-targeting antioxidants such as MitoQ) could be a special target for AD treatment. Another targets are the UPR cascade proteins (PERK, IRE1, ATF6) and receptors involved in Ca²⁺ -level stabilization of the ER (Ryr, IP3R).

Cite this article as:

Katalin Volgyi, Gábor Juhász, Zsolt Kovacs and Botond Penke , Dysfunction of Endoplasmic Reticulum (ER) and Mitochondria (MT) in Alzheimer's Disease: The Role of the ER-MT Cross-Talk, Current Alzheimer Research 2015; 12 (7) . https://dx.doi.org/10.2174/1567205012666150710095035