Mitochondrial Dysfunction and Alzheimer’s Disease

Albrekkan, Fatimah M.; Kelly-Worden, Marie

doi:10.4236/ojemd.2013.32a003

Cited by 8 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ca 2+ dysregulation has been implicated in MD as well as defective apoptotic pathways and is associated with several classes of diseases, including cancer, autoimmune diseases, and neurodegenerative diseases [6] [7]. As previously mentioned, DMD is characterized by a deficiency of the dystrophin protein which is believed to eventually lead to increased Ca 2+ permeability into muscle cells [4].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction in Duchenne Muscular Dystrophy

Kelly-Worden¹,

Thomas²

2014

OJEMD

Self Cite

View full text Add to dashboard Cite

Muscular Dystrophy (MD) is an X-linked recessive disease affecting mainly boys at a rate of 1 in every 3500 live births. The most common and severe form of the disease is Duchenne Muscular Dystrophy (DMD). The disease is characterized by a relatively rapid wasting of skeletal muscle tissue to a point that leads to paralysis in all patients that suffer from the disease. Unfortunately, due to respiratory or cardiac muscle failure, death occurs in most patients around the age of 30. Currently, the lack of the protein dystrophin is thought to be the chief cause of disease in DMD patients. In addition to a lack of dystrophin, studies are emerging that are painting a picture of a more intricate connection between mitochondrial dysfunction and DMD where increased intracellular and inter-mitochondrial calcium has been shown to cause mitochondrial swelling, loss of mitochondrial membrane integrity, cell death and muscle atrophy. In this article, we will discuss the evidence that places the mitochondrion as a central participant in the etiology of DMD and describe how the relationship between increased intracellular calcium, mitochondrial permeability and dysfunction culminates in muscle loss.

show abstract

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction in Duchenne Muscular Dystrophy

Kelly-Worden¹,

Thomas²

2014

OJEMD

Self Cite

View full text Add to dashboard Cite

show abstract

“…Partial inhibition of the mitochondrial respiratory chain produces free radicals, diminishes aerobic energy metabolism and causes excitotoxic damage that creates a deleterious spiral leading to neurodegeneration [15] . NaN 3 neurotoxicity has been explored in recapitulating behavioral and pathological features of AD [16,17] .…”

Section: Introductionmentioning

confidence: 99%

Cerebellar Molecular and Cellular Characterization in Rat Models of Alzheimer's Disease: Neuroprotective Mechanisms of <b><i>Garcinia</i></b> Biflavonoid Complex

et al. 2017

View full text Add to dashboard Cite

Background: Recent evidences suggest that cerebellar degeneration may be associated with the development of Alzheimer's disease (AD). However, previous reports were mainly observational, lacking substantial characterization of cellular and molecular cerebellar features during AD progression. Purpose: This study is aimed at characterizing the cerebellum in rat models of AD and assessing the corresponding neuroprotective mechanisms of Garcinia biflavonoid complex (GBc). Methods: Male Wistar rats were grouped and treated alone or in combination with PBS (ad libitum)/day, corn oil (CO; 2 mL/kgBw/day), GBc (200 mg/kgBw/day), sodium azide (NaN₃) (15 mg/kgBw/day) and aluminium chloride (AlCl₃) (100 mg/kgBw/day). Groups A and B received PBS and CO, respectively; C received GBc; D received NaN₃; E received AlCl₃; F received NaN₃ then GBc subsequently; G received AlCl₃ then GBc subsequently; H received NaN₃ and GBc simultaneously while I received AlCl₃ and GBc simultaneously. Following treatments, cerebellar cortices were processed for histology, immunohistochemistry and colorimetric assays. Results: Our data revealed that cryptic granule neurons and pyknotic Purkinje cell bodies (characterized by short dendritic/axonal processes) correspond to indistinctly demarcated cerebellar layers in rats treated with AlCl₃ and NaN₃. These correlates, with observed hypertrophic astrogliosis, increased the neurofilament deposition, depleted the antioxidant system-shown by expressed superoxide dismutase and glutathione peroxidase, and cerebellar glucose bioenergetics dysfunction-exhibited in assayed lactate dehydrogenase and glucose-6-phosphate dehydrogenase. We further showed that GBc reverses cerebellar degeneration through modulation of neurochemical signaling pathways and stressor molecules that underlie AD pathogenesis. Conclusion: Cellular, molecular and metabolic neurodegeneration within the cerebellum is associated with AlCl₃ and NaN₃-induced AD while GBc significantly inhibits corresponding neurotoxicity and is more efficacious when pre-administered.

show abstract

“…Under these conditions hyperphosphorylation of tau seems to be independent of GSK3ß kinase activity. This cycle has been proposed as the "mitochondrial cascade hypothesis" [74,75]. Since mitochondrial dysfunction and ROS production are general hallmarks of the aging process, the hypothesis may also explain the increased incidence of AD with age.…”

Section: Aging Energy Mitochondria and Oxidative Stressmentioning

confidence: 99%

Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells

Heinisch¹,

Brandt²

2016

MIC

View full text Add to dashboard Cite

In the past decade, yeast have been frequently employed to study the molecular mechanisms of human neurodegenerative diseases, generally by means of heterologous expression of genes encoding the relevant hallmark proteins. However, it has become evident that substantial posttranslational modifications of many of these proteins are required for the development and progression of potentially disease relevant changes. This is exemplified by the neuronal tau proteins, which are critically involved in a class of neurodegenerative diseases collectively called tauopathies and which includes Alzheimer's disease (AD) as its most common representative. In the course of the disease, tau changes its phosphorylation state and becomes hyperphosphorylated, gets truncated by proteolytic cleavage, is subject to O-glycosylation, sumoylation, ubiquitinylation, acetylation and some other modifications. This poses the important question, which of these posttranslational modifications are naturally occurring in the yeast model or can be reconstituted by heterologous gene expression. Here, we present an overview on common modifications as they occur in tau during AD, summarize their potential relevance with respect to disease mechanisms and refer to the native yeast enzyme orthologs capable to perform these modifications. We will also discuss potential approaches to humanize yeast in order to create modification patterns resembling the situation in mammalian cells, which could enhance the value of Saccharomyces cerevisiae and Kluyveromyces lactis as disease models.

show abstract

Mitochondrial Dysfunction and Alzheimer’s Disease

Cited by 8 publications

References 23 publications

Mitochondrial Dysfunction in Duchenne Muscular Dystrophy

Mitochondrial Dysfunction in Duchenne Muscular Dystrophy

Cerebellar Molecular and Cellular Characterization in Rat Models of Alzheimer's Disease: Neuroprotective Mechanisms of <b><i>Garcinia</i></b> Biflavonoid Complex

Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells

Contact Info

Product

Resources

About