Fibrillar beta-amyloid (Aβ) (1–42) elevates extracellular Aβ in cultured hippocampal neurons of adult rats

Majd, Shohreh; Rastegar, Karim; Zarifkar, Asadollah; Takhshid, Mohammad Ali

doi:10.1016/j.brainres.2007.09.033

Cited by 13 publications

(10 citation statements)

References 45 publications

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“…The primary adult neuron culture was carried out according to the methods described previously (Brewer and Torricelli 2007;Majd et al 2007). The pellet was resuspended in 6 ml of B27, NeuroBasalA, 0.5 mM Glutamax and 5 ng/ml FGF2.…”

Section: Primary Adult Neuronsmentioning

confidence: 99%

Effects of proNGF on Neuronal Viability, Neurite Growth and Amyloid-beta Metabolism

et al. 2009

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Alzheimer's disease (AD) is characterized pathologically by the deposition of amyloid-beta peptides (Abeta), neurofibrillary tangles, distinctive neuronal loss and neurite dystrophy. Nerve growth factor (NGF) has been suggested to be involved in the pathogenesis of AD, however, the role of its precursor (proNGF) in AD remains unknown. In this study, we investigated the effect of proNGF on neuron death, neurite growth and Abeta production, in vitro and in vivo. We found that proNGF promotes the death of different cell lines and primary neurons in culture, likely dependent on the expression of p75(NTR). We for the first time found that proNGF has an opposite role in neurite growth to that of mature NGF, retarding neurite growth in both cell lines and primary neurons. proNGF is localized to the Abeta plaques in AD mice brain, however, it had no significant effect on Abeta production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.

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Section: Primary Adult Neuronsmentioning

confidence: 99%

Effects of proNGF on Neuronal Viability, Neurite Growth and Amyloid-beta Metabolism

et al. 2009

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“…Apoptosis can contribute to disorders such as diabetes [13,14,15,16], tissue ischemia [17,18,19,20], bone fatigue [21], Alzheimer's disease [22,23,24,25,26,27,28,29,30,31,32], neurodegenerative disorders [33,34,35,36], plasticity associated with ischemic preconditioning [37], aging-related diseases [38,39,40], and toxic conditions during development [41,42]. The pathology with these disorders can be linked to mitochondrial dysfunction [43,44,45,46], especially during metabolic disorders [47] and Alzheimer’s disease [48], that ultimately can lead to cell death in a variety of cells such as neurons, endothelial cells (ECs), cardiomyocytes, and smooth muscle cells [32,49,50,51,52,53].…”

Section: Nicotinamide Oxidative Stress and Cellular Survivalmentioning

confidence: 99%

The Vitamin Nicotinamide: Translating Nutrition into Clinical Care

et al. 2009

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Nicotinamide, the amide form of vitamin B3 (niacin), is changed to its mononucleotide compound with the enzyme nicotinic acide/nicotinamide adenylyl-transferase, and participates in the cellular energy metabolism that directly impacts normal physiology. However, nicotinamide also influences oxidative stress and modulates multiple pathways tied to both cellular survival and death. During disorders that include immune system dysfunction, diabetes, and aging-related diseases, nicotinamide is a robust cytoprotectant that blocks cellular inflammatory cell activation, early apoptotic phosphatidylserine exposure, and late nuclear DNA degradation. Nicotinamide relies upon unique cellular pathways that involve forkhead transcription factors, sirtuins, protein kinase B (Akt), Bad, caspases, and poly (ADP-ribose) polymerase that may offer a fine line with determining cellular longevity, cell survival, and unwanted cancer progression. If one is cognizant of the these considerations, it becomes evident that nicotinamide holds great potential for multiple disease entities, but the development of new therapeutic strategies rests heavily upon the elucidation of the novel cellular pathways that nicotinamide closely governs.

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“…Oxidative stress results in cell injury through apoptotic and nonapoptotic pathways. In regard to programmed cell death (apoptosis), apoptosis can occur during DM, 2 , 3 , 120 , 121 anesthetic exposure, 122 tissue ischemia, 123 – 126 bone fatigue, 127 neurodegenerative disorders, 34 , 128 – 130 Alzheimer's disease, 51 – 54 , 59 , 131 – 136 plasticity associated with ischemic preconditioning, 137 aging‐related diseases, 35 , 138 , 139 and toxic conditions during development 122 , 140 …”

Section: Oxidative Stress Apoptotic Injury Mitochondria and Diabetesmentioning

confidence: 99%

Novel Avenues of Drug Discovery and Biomarkers for Diabetes Mellitus

Maiese

Chong

Shang

et al. 2011

The Journal of Clinical Pharmacology

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Globally, developed nations spend a significant amount of their resources on healthcare initiatives that poorly translate into increased population life expectancy. As an example, the United States devotes sixteen percent of its gross domestic product to healthcare, the highest level in the world, but falls behind other nations that enjoy greater individual life expectancy. These observations point to the need for pioneering avenues of drug discovery to increase lifespan with controlled costs. In particular, innovative drug development for metabolic disorders such as diabetes mellitus (DM) becomes increasingly critical given that the number of diabetic individuals will increase exponentially over the next twenty years. Here we discuss the elucidation and targeting of novel cellular pathways that are intimately tied to oxidative stress in DM for new treatment strategies. Pathways that involve wingless, NAD + precursors, and cytokines govern complex biological pathways that determine both cell survival and longevity during DM and its complications. Furthermore, the role of these entities as biomarkers for disease can further enhance their utility irrespective of their treatment potential. Greater understanding of the intricacies of these unique cellular mechanisms will shape future drug discovery for DM to provide focused clinical care with limited or absent long-term complications. Keywords biomarkers; diabetes; oxidative stress Healthcare and metabolic diseaseCompared with other nations throughout the world, the United States devotes 16% of the gross domestic product to healthcare and spending for each individual equal to $7,290, the highest levels in the world 1 . Total spending on pharmaceuticals is also the highest in the world with $878 per individual. Yet, life expectancy in years in the United States equals 78.1 years and trails behind other countries such as Japan that allots 8% of the gross domestic product on healthcare, spends $2,514 for each individual, and has a life expectancy of 82.6 years. Furthermore, the United States is ranked as having the highest level of obesity in the population at 34.3% while countries such as Japan have a 3.4% level of obesity 1 . These statistics are the results of multiple factors, but also can support the arguments for not only improved preventive health measures, but also new directions to treat multiple disorders that can lead to improved lifespan while minimizing economic burden.In particular, one can consider diabetes mellitus (DM), a metabolic disorder closely associated with increased weight gain 2,3 . DM reaches approximately 20 million individuals in the United States and more than 165 million individuals worldwide 4 . By 2030, DM may affect more than 360 million individuals. Additionally, a significant portion of the population has undiagnosed diabetes, illustrating the need for improved early diagnosis 5 . The incidence of impaired glucose tolerance in the young also raises further concerns 6 . Individuals with impaired glucose tolerance have a greate...

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Fibrillar beta-amyloid (Aβ) (1–42) elevates extracellular Aβ in cultured hippocampal neurons of adult rats

Cited by 13 publications

References 45 publications

Effects of proNGF on Neuronal Viability, Neurite Growth and Amyloid-beta Metabolism

Effects of proNGF on Neuronal Viability, Neurite Growth and Amyloid-beta Metabolism

The Vitamin Nicotinamide: Translating Nutrition into Clinical Care

Novel Avenues of Drug Discovery and Biomarkers for Diabetes Mellitus

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