Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in Alzheimer's disease and Parkinson's disease

被引:223
作者
Ganguly, Gargi [1 ]
Chakrabarti, Sasanka [2 ]
Chatterjee, Uttara [1 ]
Saso, Luciano [3 ]
机构
[1] Inst Post Grad Med Educ & Res, Dept Pathol, Kolkata, India
[2] ICARE Inst Med Sci & Res, Dept Biochem, Haldia 721645, W Bengal, India
[3] Sapienza Univ Rome, Dept Physiol & Pharmacol Vittorio Erspamer, Rome, Italy
关键词
proteinopathy; amyloid beta; oxidative stress; alpha-synuclein; mitochondrial dysfunction; AMYLOID-BETA-PEPTIDE; ALPHA-SYNUCLEIN AGGREGATION; COMPLEX I DEFICIENCY; PRECURSOR PROTEIN; A-BETA; SUBSTANTIA-NIGRA; NADPH OXIDASE; TRANSCRIPTIONAL REGULATION; HYPERPHOSPHORYLATED TAU; PROTECTIVE ROLE;
D O I
10.2147/DDDT.S130514
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Alzheimer's disease and Parkinson's disease are two common neurodegenerative diseases of the elderly people that have devastating effects in terms of morbidity and mortality. The predominant form of the disease in either case is sporadic with uncertain etiology. The clinical features of Parkinson's disease are primarily motor deficits, while the patients of Alzheimer's disease present with dementia and cognitive impairment. Though neuronal death is a common element in both the disorders, the postmortem histopathology of the brain is very characteristic in each case and different from each other. In terms of molecular pathogenesis, however, both the diseases have a significant commonality, and proteinopathy (abnormal accumulation of misfolded proteins), mitochondrial dysfunction and oxidative stress are the cardinal features in either case. These three damage mechanisms work in concert, reinforcing each other to drive the pathology in the aging brain for both the diseases; very interestingly, the nature of interactions among these three damage mechanisms is very similar in both the diseases, and this review attempts to highlight these aspects. In the case of Alzheimer's disease, the peptide amyloid beta (A beta) is responsible for the proteinopathy, while alpha-synuclein plays a similar role in Parkinson's disease. The expression levels of these two proteins and their aggregation processes are modulated by reactive oxygen radicals and transition metal ions in a similar manner. In turn, these proteins - as oligomers or in aggregated forms - cause mitochondrial impairment by apparently following similar mechanisms. Understanding the common nature of these interactions may, therefore, help us to identify putative neuroprotective strategies that would be beneficial in both the clinical conditions.
引用
收藏
页码:797 / 810
页数:14
相关论文
共 151 条
[1]  
a Armstrong R., 2011, International journal of Alzheimer's disease, V2011, P1
[2]   β-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase [J].
Abramov, AY ;
Canevari, L ;
Duchen, MR .
JOURNAL OF NEUROSCIENCE, 2004, 24 (02) :565-575
[3]   Oxidative Stress-Mediated Regulation of Proteasome Complexes [J].
Aiken, Charity T. ;
Kaake, Robyn M. ;
Wang, Xiaorong ;
Huang, Lan .
MOLECULAR & CELLULAR PROTEOMICS, 2011, 10 (05)
[4]   Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules [J].
Alonso, AD ;
GrundkeIqbal, I ;
Iqbal, K .
NATURE MEDICINE, 1996, 2 (07) :783-787
[5]   Overexpression of alpha-synuclein at non-toxic levels increases dopaminergic cell death induced by copper exposure via modulation of protein degradation pathways [J].
Anandhan, Annadurai ;
Rodriguez-Rocha, Humberto ;
Bohovych, Iryna ;
Griggs, Amy M. ;
Zavala-Flores, Laura ;
Reyes-Reyes, Elsa M. ;
Seravalli, Javier ;
Stanciu, Lia A. ;
Lee, Jaekwon ;
Rochet, Jean-Christophe ;
Khalimonchuk, Oleh ;
Franco, Rodrigo .
NEUROBIOLOGY OF DISEASE, 2015, 81 :76-92
[6]  
[Anonymous], 2015, ADV MAT SCI ENG, DOI DOI 10.1155/2015/701940
[7]   Aβ ion channels.: Prospects for treating Alzheimer's disease with Aβ channel blockers [J].
Arispe, Nelson ;
Diaz, Juan C. ;
Simakova, Olga .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2007, 1768 (08) :1952-1965
[8]   α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson's disease [J].
Banerjee, Kalpita ;
Sinha, Maitrayee ;
Pham, Chi Le Lan ;
Jana, Sirsendu ;
Chanda, Dalia ;
Cappai, Roberto ;
Chakrabarti, Sasanka .
FEBS LETTERS, 2010, 584 (08) :1571-1576
[9]   Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests [J].
Bates, K. A. ;
Verdile, G. ;
Li, Q. -X ;
Ames, D. ;
Hudson, P. ;
Masters, C. L. ;
Martins, R. N. .
MOLECULAR PSYCHIATRY, 2009, 14 (05) :469-486
[10]   HYDROGEN-PEROXIDE MEDIATES AMYLOID-BETA PROTEIN TOXICITY [J].
BEHL, C ;
DAVIS, JB ;
LESLEY, R ;
SCHUBERT, D .
CELL, 1994, 77 (06) :817-827