Systemic and Brain Metabolic Dysfunction as a New Paradigm for Approaching Alzheimer’s Dementia

Giordano, Vincenzo; Peluso, Gianfranco; Iannuccelli, M; Benatti, Paola; Nicolai, Raffaella; Calvani, Menotti

doi:10.1007/s11064-006-9125-8

Cited by 41 publications

(33 citation statements)

References 171 publications

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“…Emerging evidence suggests that APN plays an important role in Alzheimer's disease (AD) [4]. Consistent with this view, we recently showed that APN modulates a metabolic pathway to suppress neurodegeneration in cellular and mouse models of ␣-synucleinopathies, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB) [5].…”

Section: Introductionsupporting

confidence: 57%

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

Waragai

Adame

Trinh

et al. 2016

JAD

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Abstract. Adiponectin (APN) is protective in animal models of neurodegenerative diseases, but the role of APN in human brain has not been established. Using an enzyme-linked immunosorbent assay, we found that APN was significantly decreased in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), compared to those in patients with mild cognitive impairment (MCI) and in normal controls (NC), despite elevation of APN in serum of patients with MCI and AD compared to that in NC. The discrepancy of CSF APN from serum APN in AD may suggest some critical actions of APN in the pathogenesis of AD. Indeed, it was histologically observed that APN was co-localized with tau in neurofibrillary tangles and immunoblot analysis showed that the functional trimers of APN were significantly decreased in AD compared to those in NC. Collectively, a loss of function of APN may be involved in the pathogenesis of AD.

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Section: Introductionsupporting

confidence: 57%

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

Waragai

Adame

Trinh

et al. 2016

JAD

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“…NBM has also been reported to participate in memory and sleep/wake regulation [41, 42] and to degenerate in Alzheimer’s disease [6]. Furthermore, clinical and epidemiological studies have proposed a link between obesity/type 2 diabetes and the risk of developing Alzheimer’s disease [8, 43]. The presence of AdipoR1, as was demonstrated in our study, and the previously reported expression of leptin receptors [44] in NBM may suggest possible effects of adipocytokines on cognitive brain functions and a role in the reported obesity-linked risk for dementia.…”

Section: Discussionmentioning

confidence: 99%

Expression of Adiponectin and Adiponectin Receptors in Human Pituitary Gland and Brain

Psilopanagioti¹,

Papadaki²,

et al. 2008

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Background/Aims: Adiponectin and its receptors, AdipoR1 and AdipoR2, constitute integral components of energy homeostatic mechanism in peripheral tissues. Recent studies have implicated adiponectin in central neural networks regulating food intake and energy expenditure. The present study aimed at investigating the possible expression and distribution of adiponectin and its receptors in human pituitary gland, hypothalamus and different brain areas. Methods: Sections of the pituitary gland, hypothalamus and adjacent basal forebrain area, cerebrum and cerebellum from 35 autopsy cases, were examined using HE, PAS-Orange G, luxol fast blue/cresyl violet stains and single and double immunohistochemistry using adiponectin, AdipoR1, AdipoR2, choline acetyltransferase, FSH, LH, TSH, GH, ACTH and prolactin-specific antibodies. Age and BMI mean values ± SD of the autopsy cases were 56 ± 18 years and 27 ± 5 kg/m², respectively. Results: Strong adiponectin expression was observed in pituitary gland. In pars distalis (PD), adiponectin localized in GH, FSH, LH and TSH-producing cells and in pars tuberalis (PT) in FSH, LH and TSH-producing cells. Strong to moderate expression of AdipoR1 and AdipoR2 was observed in PD by the same cell types as adiponectin. No immunoreactivity for adiponectin receptors was noted in cells of PT. Intense AdipoR1 immunostaining was observed in neurons of lateral hypothalamic area and of nucleus basalis of Meynert (NBM). Conclusions: Adiponectin and its receptors expression in human pituitary might indicate the existence of a local system, modulating endocrine axes. Furthermore, the presence of AdipoR1 in hypothalamus and NBM suggests that adiponectin may participate in central neural signaling pathways controlling energy homeostasis and higher brain functions.

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“…It has been disclosed a different approach Alzheimer's disease neurodegeneration understanding not only by the means of neurochemistry but also biochemistry opening new scenarios in the direction of a metabolic system degeneration [93]. For example, aconitase and ATP synthase are targets of MDA modification [94]; methylglyoxal is an inhibitor of antioxidant enzymes [95] and it changes structure and function of ceruloplasmin, a serum oxidase carrier of copper ions [96].…”

Section: Discussionmentioning

confidence: 99%

Shortage of Lipid-radical Cycles in Membranes as a Possible Prime Cause of Energetic Failure in Aging and Alzheimer Disease

Dmitriev

2007

Neurochem Res

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Polyunsaturated fatty acids (PUFA) and alpha-tocopherol (alpha-TOH) are the most oxygen-sensitive constituents of cells. alpha-TOH is a member of the vitamin E family that is considered the most important lipophilic antioxidant in cell membranes. Its importance is emphasized by the involvement of oxidative stress in injury to the central nervous system and neurodegenerative diseases. Currently, alpha-TOH transfer protein (TTP), is believed to play a significant role in maintaining the vitamin status but the presence of alpha-TOH in membranes is required but not sufficient to protect the membranes against lipid hydroperoxides (LOOH) formation. The lipid-radical theory presented in this review considers the role of two membrane factors--alpha-tocopherol and cytochrome b5; these factors secure the functioning of lipid-radical cycles and the participation of lipid-radical reactions in the key membrane processes. The prominent intermembrane reaction realized via a protein-lipid interaction, during which electron transport from cytochrome b5--located in the outer membrane--to peroxyl radical (LOO*)--located in inner membrane--causes reduction of the peroxyl radical: cyt.b5red + LOO* --> cyt.b5ox + LOO(-). This secures an interaction of alpha-TOH with other intermediate, LOO(- )excepting the LOOH formation. The discussion will be focused on the consequences of ineffective electron transfer to LOO* and excessive oxidative pathway of metabolism of the PUFA (LOO* --> LOOH). Assuming the operation of cytochrome b5/alpha-tocopherol-controlled lipid-radical cycles and considering the role of the cycles in membrane bioenergetics we arrive at a model for effective function of adenine nucleotide translocator and ATP synthesis in mitochondria. This paper summarizes our experimental evidence that the oxidative and non-oxidative pathways of metabolism of PUFA via their respective intermediates occur in the cells. While this fact is not widely appreciated it may be relevant to elucidation of new mechanisms of neurodegenerative diseases.

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Systemic and Brain Metabolic Dysfunction as a New Paradigm for Approaching Alzheimer’s Dementia

Cited by 41 publications

References 171 publications

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

Expression of Adiponectin and Adiponectin Receptors in Human Pituitary Gland and Brain

Shortage of Lipid-radical Cycles in Membranes as a Possible Prime Cause of Energetic Failure in Aging and Alzheimer Disease

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