Region-specific mRNA expression of phosphatidylinositol 3-kinase regulatory isoforms in the central nervous system of C57BL/6J mice

Hörsch, Dieter; Kahn, C. Ronald

doi:10.1002/(sici)1096-9861(19991206)415:1<105::aid-cne8>3.0.co;2-h

Cited by 37 publications

(17 citation statements)

References 49 publications

(91 reference statements)

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“…The expression of other downstream effectors, such as phosphoinositide 3‐kinase (PI3K), AKT (an important kinase in signaling), and glycogen synthase kinase‐3 (GSK‐3) in the brain, presents a classical pattern that is similar to the one related to insulin in peripheral tissues. The evidence suggests that the presence of active insulin signals transduction in brain regions closely associated with cognition and synaptic function (Horsch & Kahn, ; Leroy & Brion, ).…”

Section: Alzheimer Diseasementioning

confidence: 99%

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Rojas-Gutierrez

Muñoz-Arenas

Treviño

et al. 2017

Synapse

149

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Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome, and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage. Accumulating evidence suggests that AD is closely related to a dysfunction of both insulin signaling and glucose metabolism in the brain, leading to an insulin-resistant brain state. Four drugs are currently used for this pathology: Three FDA-approved cholinesterase inhibitors and one NMDA receptor antagonist. However, wide varieties of antioxidants are promissory to delay or prevent the symptoms of AD and may help in treating the disease. Therefore, therapeutic efforts to achieve attenuation of oxidative stress could be beneficial in AD treatment, attenuating Aβ-induced neurotoxicity and improve neurological outcomes in AD. The term inflammaging characterizes a widely accepted paradigm that aging is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses in the absence of overt infection, and is a highly significant risk factor for both morbidity and mortality in the elderly.

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Section: Alzheimer Diseasementioning

confidence: 99%

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Rojas-Gutierrez

Muñoz-Arenas

Treviño

et al. 2017

Synapse

149

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“…They are expressed in numerous brain regions, namely in the olfactory bulb, hypothalamus, cerebral cortex, cerebellum, and hippocampus [44, 47, 48]. Even wider insulin receptor distribution overlaps with expression of downstream proteins and isoforms in insulin-related pathways [44, 49]. The insulin/IGF-1-mediated signaling pathways play a central role in several critical processes including cognition [50, 51], energy homeostasis [52, 53], food intake [54], neuron-astrocyte signaling [55, 56], synapse formation, and neuronal survival [50].…”

Section: Insulin a Key Neuromodulator In The Brainmentioning

confidence: 99%

Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke

Lioutas

Alfaro-Martinez

Bedoya

et al. 2015

Transl. Stroke Res.

100

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Treatment options for stroke remain limited. Neuroprotective therapies, in particular, have invariably failed to yield the expected benefit in stroke patients, despite robust theoretical and mechanistic background and promising animal data. Insulin and insulin-like growth factor 1 (IGF-1) play a pivotal role in critical brain functions, such as energy homeostasis, neuronal growth, and differentiation. They may exhibit neuroprotective properties in acute ischemic stroke based upon their vasodilatory, anti-inflammatory and antithrombotic effects, as well as improvements of functional connectivity, neuronal metabolism, neurotransmitter regulation, and remyelination. Intranasally administered insulin has demonstrated a benefit for prevention of cognitive decline in older people, and IGF-1 has shown potential benefit to improve functional outcomes in animal models of acute ischemic stroke. The intranasal route presents a feasible, tolerable, safe, and particularly effective administration route, bypassing the blood–brain barrier and maximizing distribution to the central nervous system (CNS), without the disadvantages of systemic side effects and first-pass metabolism. This review summarizes the neuroprotective potential of intranasally administered insulin and IGF-1 in stroke patients. We present the theoretical background and pathophysiologic mechanisms, animal and human studies of intranasal insulin and IGF-1, and the safety and feasibility of intranasal route for medication administration to the CNS.

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“…Most neurons express all five PI 3-kinase regulatory isoforms (Shin et al, 1998;Trejo and Pons, 2001). In general, the mRNAs for p85␣, p50␣, p55␣ AS53, and p85␤ are widespread, with the highest level in the olfactory system, neuronal groups of the forebrain and hypothalamus, the hippocampus, cortex, inferior and superior colliculus, pituitary, and cerebellum (Horsch and Kahn, 1999). Abundant mRNA expression of p55␥ (PIK) is limited to cerebellum and anterior pituitary, with moderate levels in the olfactory bulb and hippocampus, and low levels elsewhere.…”

Section: Pi 3-kinase Expressionmentioning

confidence: 99%

Functions of PI 3‐kinase in development of the nervous system

Rodgers

Theibert

2002

Intl J of Devlp Neuroscience

145

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In the nervous system, receptor regulated phosphoinositide (PI) 3-kinases (PI 3-kinases) participate in fundamental cellular activities that underlie development. Activated by trophic factors, growth factors, neuregulins, cytokines, or neurotransmitters, PI 3-kinases have been implicated in neuronal and glial survival and differentiation. PI 3-kinases produce inositol lipid second messengers that bind to pleckstrin homology (PH) domains in diverse groups of signal transduction proteins, and control their enzymatic activities, subcellular membrane localization, or both. Downstream targets of the inositol lipid messengers include protein kinases and regulators of small GTPases. The kinase Akt/PKB functions as a key component of the PI 3-kinase dependent survival pathway through its phosphorylation and regulation of apoptotic proteins and transcription factors. Furthermore, since members of the Rho GTPase and Arf GTPase families have been implicated in regulation of the actin cytoskeleton, vesicular trafficking, and transcription, the downstream targets of PI 3-kinase that control these GTPases are excellent candidates to mediate aspects of PI 3-kinase dependent neuronal and glial differentiation.

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Region-specific mRNA expression of phosphatidylinositol 3-kinase regulatory isoforms in the central nervous system of C57BL/6J mice

Cited by 37 publications

References 49 publications

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke

Functions of PI 3‐kinase in development of the nervous system

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