Alzheimer's Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia

被引:91
|
作者
Eshraghi, Mehdi [1 ,2 ]
Adlimoghaddam, Aida [3 ]
Mahmoodzadeh, Amir [4 ]
Sharifzad, Farzaneh [5 ]
Yasavoli-Sharahi, Hamed [5 ]
Lorzadeh, Shahrokh [6 ]
Albensi, Benedict C. [3 ,7 ]
Ghavami, Saeid [6 ,8 ,9 ,10 ]
机构
[1] Columbia Univ, Ctr Motor Neuron Biol & Dis, New York, NY 10032 USA
[2] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA
[3] St Boniface Hosp Albrechtsen Res Ctr, Div Neurodegenerat Disorders, Winnipeg, MB R2H 2A6, Canada
[4] Kermanshah Univ Med Sci, Hlth Technol Inst, Med Biol Res Ctr, Kermanshah 6734667149, Iran
[5] Univ Ottawa, Dept Cellular & Mol Med, Fac Med, Ottawa, ON K1H 8M5, Canada
[6] Univ Manitoba, Dept Human Anat & Cell Sci, Rady Fac Hlth Sci, Max Rady Coll Med, Winnipeg, MB R3E 0J9, Canada
[7] Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB R3T 2N2, Canada
[8] Canc Care Manitoba Univ Manitoba, Res Inst Oncol & Hematol, Winnipeg, MB R3E 0V9, Canada
[9] Univ Manitoba, Biol Breathing Theme, Children Hosp Res Inst Manitoba, Winnipeg, MB R3E 0V9, Canada
[10] Katowice Sch Technol, Fac Med, PL-40555 Katowice, Poland
关键词
mitochondria; inflammation; autophagy; mitophagy; microglia; Alzheimer’ s; neurodegeneration; neuroinflammation; AMYLOID-BETA-PEPTIDE; CENTRAL-NERVOUS-SYSTEM; POTENTIAL THERAPEUTIC TARGET; GLYCATION END-PRODUCTS; BLOOD-BRAIN-BARRIER; KAPPA-B ACTIVATION; MOUSE MODEL; A-BETA; MITOCHONDRIAL DYSFUNCTION; APOLIPOPROTEIN-E;
D O I
10.3390/ijms22073330
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer's disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including amyloid plaques (A beta) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.
引用
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页数:36
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