Mitochondrial Dysfunction: The First Domino in Brain Aging and Alzheimer's Disease?

Abstract

With the increasing average life span of humans and with decreasing cognitive function in elderly individuals, age-related cognitive disorders including dementia have become a major health problem in society. Aging-related mitochondrial dysfunction underlies many common neurodegenerative disorders diseases, including Alzheimer's disease (AD). AD is characterized by two major histopathological hallmarks, initially intracellular and with the progression of the disease extracellular accumulation of oligomeric and fibrillar beta-amyloid (Abeta) peptides and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein. In this review, the authors focus on the latest findings in AD animal models indicating that these histopathological alterations induce deficits in the function of the complexes of the respiratory chain and therefore consecutively result in mitochondrial dysfunction. This parameter is intrinsically tied to oxidative stress. Both are early events in aging and especially in the pathogenesis of aging-related severe neurodegeneration. Ginkgo biloba extract seems to be of therapeutic benefit in the treatment of mild to moderate dementia of different etiology, although the data are quite heterogeneous. Herein, the authors suggest that mitochondrial protection and subsequent reduction of oxidative stress are important components of the neuroprotective activity of Ginkgo biloba extract.

Erythropoietin: Elucidating new cellular targets that broaden therapeutic strategies

“…Loss of ΔΨ m through the opening of the mitochondrial permeability transition pore represents a significant determinant for cell injury and the subsequent induction of apoptosis (Leuner et al, 2007;. EPO has the capacity to prevent the depolarization of the mitochondrial membrane that also affects the release of cytochrome c (Chong et al, 2002b;Chong et al, 2003e;Miki et al, 2006).…”

“…In fact, it has recently been shown that genes involved in the apoptotic process are replicated early during processes that involve cell replication and transcription, suggesting a much broader role for these genes than originally anticipated (Cohen et al, 2007). Apoptotic induced oxidative stress in conjunction with processes of mitochondrial dysfunction can contribute to a variety of disease states such as diabetes, ischemia, general cognitive loss, Alzheimer's disease, and trauma (Chong et al, 2005e;f;Harris et al, 2007;Leuner et al, 2007;Okouchi et al, 2007). Oxidative stress can lead to apoptosis in a variety of cell types that involve neurons, ECs, cardiomyocytes, and smooth muscle cells through multiple cellular pathways Harris et al, 2007;Kang et al, 2003b;Karunakaran et al, 2007;Verdaguer et al, 2007).…”

Erythropoietin and Oxidative Stress

“…It has recently been shown that genes involved in the apoptotic process are replicated early during processes that involve cell replication and transcription, suggesting a much broader role for these genes than originally anticipated (Cohen, et al, 2007). Apoptotic induced oxidative stress in conjunction with processes of mitochondrial dysfunction can contribute to a variety of disease states such as diabetes, ischemia, general cognitive loss, Alzheimer's disease, and trauma (Chong, et al, 2005e, Chong, et al, 2005f, Harris, et al, 2007, Leuner, et al, 2007, Okouchi, et al, 2007. Oxidative stress can lead to apoptosis in a variety of cell types that involve neurons, endothelial cells (ECs), cardiomyocytes, and smooth muscle cells through multiple cellular pathways , Harris, et al, 2007, Karunakaran, et al, 2007, Verdaguer, et al, 2007.…”

Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function.

“…Mitochondrial dysfunction may be an early event in the pathogenesis of AD [121][122][123]. AD patients show impairments in mitochondrial function that start early in process of neurodegeneration [121,123].…”