Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

Reddy, P. Hemachandra; Reddy, T. P.

doi:10.2174/156720511795745401

Cited by 200 publications

(150 citation statements)

References 171 publications

(232 reference statements)

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“…Because ROS and mitochondrial dysfunction are two of the primary pathological features of AD [20] and are widely implicated in STZ-induced cell death [21] , we next examined whether LX2343 affected ROS accumulation in cells with antioxidant VE as a positive control [22] . As expected, ROS generation was greatly increased after STZ incubation in both SH-SY5Y (162.45%±0.043%) (Figure 2A, 2B) and primary neuronal cells (126.35%±3.50%) ( Figure 2C, 2D), whereas 100 μmol/L VE inhibited such STZ-induced effects.…”

Section: Lx2343 Alleviated Stz-induced Os and Ameliorated Mitochondrimentioning

confidence: 99%

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

et al. 2017

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alzheimer's disease (aD) is a progressive neurodegenerative disease leading to the irreversible loss of brain neurons and cognitive abilities, and the vicious interplay between oxidative stress (OS) and tauopathy is believed to be one of the major players in aD development. Here, we demonstrated the capability of the small molecule N-(1,3-benzodioxol-5-yl)-2-[5-chloro-2-methoxy(phenylsulfonyl)anilino]acetamide (LX2343) to ameliorate the cognitive dysfunction of aD model rats by inhibiting OS-induced neuronal apoptosis and tauopathy. Streptozotocin (STZ) was used to induce OS in neuronal cells in vitro and in aD model rats that were made by intracerebroventricular injection of STZ (3 mg/kg, bilaterally), and Morris water maze test was used to evaluate the cognitive dysfunction in ICV-STZ rats. Treatment with LX2343 (5-20 μmol/L) significantly attenuated STZ-induced apoptosis in SH-SY5Y cells and mouse primary cortical neurons by alleviating OS and inhibiting the JNK/p38 and pro-apoptotic pathways. LX2343 was able to restore the integrity of mitochondrial function and morphology, increase aTP biosynthesis, and reduce ROS accumulation in the neuronal cells. In addition, LX2343 was found to be a non-ATP competitive GSK-3β inhibitor with IC 50 of 1.84±0.07 μmol/L, and it potently inhibited tau hyperphosphorylation in the neuronal cells. In ICV-STZ rats, administration of LX2343 (7, 21 mg·kg -1 ·d -1 , ip, for 5 weeks) efficiently improved their cognitive deficits. LX2343 ameliorates the cognitive dysfunction in the AD model rats by suppressing OS-induced neuronal apoptosis and tauopathy, thus highlighting the potential of LX2343 for the treatment of aD.

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Section: Lx2343 Alleviated Stz-induced Os and Ameliorated Mitochondrimentioning

confidence: 99%

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

et al. 2017

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“…Moreover, mitochondria are essential for oxidative metabolism in eukaryotic cells and represent the major contributor to energy transduction and ATP production. Not surprisingly, mitochondrial dysfunction has been associated with various diseases including metabolic disorders, neurodegenerative diseases, and cancer (1)(2)(3)(4)(5)(6)(7). In mitochondria, virtually all metabolic processes depend on NAD.…”

Section: Endogenous Nmnat3 In the Mitochondria Of Human Cellsmentioning

confidence: 99%

“…In yeast and plants, membrane carriers mediating NAD ϩ transport across the inner mitochondrial membrane have been identified. In the plant Arabidopsis thaliana, two transporter homologs, AtNDT1 and AtNDT2, 3 were shown to exhibit NAD ϩ transport activity (19). Although AtNDT1 is expressed in chloroplasts, AtNDT2 localizes to mitochondria.…”

Section: Endogenous Nmnat3 In the Mitochondria Of Human Cellsmentioning

confidence: 99%

Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells

VanLinden

Dölle

Pettersen

et al. 2015

Journal of Biological Chemistry

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“…Another common finding in chronic illness patients is mitochondrial dysfunction, characterized by loss of efficiency in the electron transport chain, reductions in mitochondrial inner membrane trans-membrane potential and reductions in the synthesis of high-energy molecules such as ATP [4][5][6]. This is also a characteristic of aging, and it essentially occurs in all chronic diseases, including cancer [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…This is also a characteristic of aging, and it essentially occurs in all chronic diseases, including cancer [5][6][7]. This review will concentrate on commonly acquired mechanisms that affect mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

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

Nicolson

Settineri

Ellithorpe³

2014

FFHD

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Background: Many chronic diseases and illnesses are associated with one or more chronic infections, dysfunction of mitochondria and reduced production of ATP. This results in fatigue and other symptoms that occur in most if not all chronic conditions and diseases.Methods: This is a review of the published literature on chronic infections in neurodegenerative diseases and fatiguing illnesses that are also typified by mitochondrial dysfunction. This contribution also reviews the use of natural supplements to enhance mitochondrial function and reduce the effects of chronic infections to improve overall function in various chronic illnesses.Results: Mitochondrial function can be enhanced by the use of various natural supplements, notably Lipid Replacement Therapy (LRT) using glyerolphospholipids and other mitochondrial supplements. In various chronic illnesses that are characterized by the presence of chronic infections, such as intracellular bacteria (Mycoplasma, Borrelia, Chlamydia and other infections) and viruses, LRT has proven useful in multiple clinical trials. For example, in clinical studies on chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses where a large majority of patients have chronic infections, LRT significantly reduced fatigue by 35-43% in different clinical trials and increased mitochondrial function. In clinical trials on patients with multiple intracellular bacterial infections and intractable fatigue LRT plus other mitochondrial supplements significantly decreased fatigue and improved mood and cognition.Conclusions: LRT formulations designed to improve mitochondrial function appear to be useful as non-toxic dietary supplements for reducing fatigue and restoring mitochondrial and other cellular membrane functions in patients with chronic illnesses and multiple chronic infections. BackgroundPatients with chronic neurodegenerative, neurobehavioral and fatiguing illnesses commonly test positive for systemic and central nervous system (CNS) bacterial and viral infections [1][2][3]. In addition, other chronic illnesses where neurological manifestations are routinely found, such as autoimmune diseases and other chronic illnesses and disorders, also show evidence of systemic bacterial and viral infections that could be important in disease inception, progression and/or enhancing the types and severities of signs and symptoms [2,3].Evidence of bacterial infections, such as Mycoplasma species, Chlamydia pneumoniae, Borrelia burgdorferi, among others, and viruses, such as human herpesvirus (HHV), cytomegalovirus (CMV), human herpes viruses (HHV) and other viral infections, have revealed high rates of infection in the illnesses listed above that were not found in control populations [1][2][3]. Although the specific roles of chronic infections in various diseases and their pathogeneses have not been carefully determined, the data suggest that chronic bacterial and/or viral infections are common features of essentially all progressive chronic diseases [1][2][3].An...

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Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

Cited by 200 publications

References 171 publications

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells

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

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