Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease

Aliev, Gjumrakch; Palacios, Hector H.; Walrafen, Brianna; Lipsitt, Amanda; Obrenovich, Mark E.; Morales, Ludis

doi:10.1016/j.biocel.2009.03.015

Cited by 94 publications

(75 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disturbance of mitochondrial dynamics leads to pathological conditions exacerbated in tissues with high metabolic demand such as neuronal or muscle tissues (3). Although it often is unclear whether defects in mitochondrial dynamics are the cause or effect of the disease, mitochondria have now emerged as drug targets for several pathologies (4,5).…”

mentioning

confidence: 99%

Listeria monocytogenes transiently alters mitochondrial dynamics during infection

Stavru

Bouillaud

Sartori

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

211

214

View full text Add to dashboard Cite

Mitochondria are essential and highly dynamic organelles, constantly undergoing fusion and fission. We analyzed mitochondrial dynamics during infection with the human bacterial pathogen Listeria monocytogenes and show that this infection profoundly alters mitochondrial dynamics by causing transient mitochondrial network fragmentation. Mitochondrial fragmentation is specific to pathogenic Listeria monocytogenes, and it is not observed with the nonpathogenic Listeria innocua species or several other intracellular pathogens. Strikingly, the efficiency of Listeria infection is affected in cells where either mitochondrial fusion or fission has been altered by siRNA treatment, highlighting the relevance of mitochondrial dynamics for Listeria infection. We identified the secreted pore-forming toxin listeriolysin O as the bacterial factor mainly responsible for mitochondrial network disruption and mitochondrial function modulation. Together, our results suggest that the transient shutdown of mitochondrial function and dynamics represents a strategy used by Listeria at the onset of infection to interfere with cellular physiology.bacterial infection | calcium influx | bioenergetics

show abstract

mentioning

confidence: 99%

Listeria monocytogenes transiently alters mitochondrial dynamics during infection

Stavru

Bouillaud

Sartori

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

211

214

View full text Add to dashboard Cite

show abstract

“…1): (1) in CNS diseases like stroke, PD, AD, ALS, with a strong glutamate excitotoxicity component, the inhibition of NOX enzymes is expected to be beneficial, while (2) when the neuroinflammatory process is mediated by peripheral immune cells, activation of NOX2 in antigen presenting cells of the immune system is predicted to bring a therapeutic effect.…”

mentioning

confidence: 99%

“…Although it has been known for a long time that mitochondria are an important source of ROS in CNS disease [113,2], the role of NOX enzymes in CNS pathologies is rapidly emerging. However, because of the presence of at least three NOX isoforms in the CNS and the absence of studies using specific NOX inhibitors, we focus here on disease models where proof-of-principle studies using knock-out or mutant mice are available.…”

mentioning

confidence: 99%

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Sorce

Krause

Jaquet

2012

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.

show abstract

“…Melatonin also activates signalling pathways, namely the Bcl-2 pathway that stabilizes mitochondrial function by antiapoptotic Bcl-2 family modulators. Melatonin enhanced Bcl-2 expression with consequent inhibition of Aβ-induced cell death [60]. Caspase-3 is known to be directly linked to cytochrome c release and is related to cell death in AD [61,62], and this is down regulated by melatonin [63].…”

Section: Molecular Mechanisms Of Melatonin's Antiamyloid Actionsmentioning

confidence: 95%

Alzheimer’s Disease: Focus on the Neuroprotective Role of Melatonin

Srinivasan¹

2012

J Neurol Res

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by a progressive loss of memory and cognitive function, and by behavioural and sleep disturbances, including insomnia. The pathophysiology of AD has been attributed to oxidative stress-induced amyloid-β protein (Aβ) deposition. Abnormal tau protein, mitochondrial dysfunction and protein hyper-phosphorylation have been demonstrated in neural tissues of AD patients. AD patients exhibit severe sleep-wake disturbances and these sleep disturbances are associated with rapid cognitive decline and memory impairment. Optimally effective management of AD patients will likely require a drug that can arrest Aβ -induced neurotoxic effects and can also restore the disturbed sleep-wake rhythm, with improvement in sleep quality. In this context, the pineal hormone melatonin has been demonstrated to be an effective antioxidant that can prevent Aβ -induced neurotoxic effects through a variety of mechanisms. Sleep deprivation itself produces many effects including oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, altered proteosomal processing and abnormal activation of enzymes. In addition to treating the signs and symptoms of AD, treatment of sleep disturbances may also be necessary for preventing and arresting AD progression. Besides melatonin, a number of melatonergic agonists such as ramelteon, agomelatine and tasimelteon are now used clinically for treating insomnia and other sleep disorders. Their use may also be beneficial in treating Alzheimer's disease.

show abstract

Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease

Cited by 94 publications

References 137 publications

Listeria monocytogenes transiently alters mitochondrial dynamics during infection

Listeria monocytogenes transiently alters mitochondrial dynamics during infection

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Alzheimer’s Disease: Focus on the Neuroprotective Role of Melatonin

Contact Info

Product

Resources

About