Abstract：
:'Metabolism' refers to the vast collection of chemical processes that occur within a living organism. Within this broad designation, one can identify metabolism events that relate specifically to energy homeostasis, whether they occur at the subcellular, cellular, organ, or whole organism level. This review operationally refers to this type of metabolism as 'energy metabolism' or 'bioenergetics.' Changes in energy metabolism/bioenergetics have been linked to brain aging and a number of neurodegenerative diseases, and research suggests mitochondria may uniquely contribute to this. Interventions that manipulate energy metabolism/bioenergetic function and mitochondria may have therapeutic potential and efforts intended to accomplish this are playing out at basic, translational, and clinical levels. This review follows evolving views of energy metabolism's role in neurodegenerative diseases but especially Alzheimer's disease, with an emphasis on the bench-to-bedside process whose ultimate goal is to develop therapeutic interventions. It further considers challenges encountered during this process, which include linking basic concepts to a medical question at the initial research stage, adapting conceptual knowledge gained to a disease-associated application in the translational stage, extending what has been learned to the clinical arena, and maintaining support for the research at each of these fundamentally linked but functionally distinct stages. A bench-to-bedside biomedical research process is discussed that moves through conceptual, basic, translational, and clinical levels. For example, herein a case was made that bioenergetics is a valid Alzheimer's disease therapeutic target. Following this, a fundamental strategy for manipulating bioenergetics was defined, potential implications studied, and the approach extended to the clinical arena. This article is part of the 60th Anniversary special issue.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Swerdlow RHdoi
10.1111/jnc.13509subject
Has Abstractpub_date
2016-10-01 00:00:00pages
126-135eissn
0022-3042issn
1471-4159journal_volume
139 Suppl 2pub_type
杂志文章,评审abstract：:At the premyelinating stage, the Schwann cells of peripheral nerves are able to recognize the axon, to arrange themselves along it in a nonoverlapping manner, and finally to establish a one-to-one cell-axon relationship. The mechanism that regulates these processes is not known in detail. We found the existence of a s...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.68051853.x
更新日期：1997-05-01 00:00:00
abstract：:Kallikrein 6 is a serine protease expressed abundantly in normal adult human and rodent CNS, and therein is regulated by injury. In the case of CNS demyelinating disease, K6 expression in CNS occurs additionally in perivascular and parenchymal inflammatory cells suggesting a role in pathogenesis. Herein we describe tw...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02826.x
更新日期：2004-12-01 00:00:00
abstract：:Three unique 5' untranslated regions (UTRs) have been characterized for human microtubule-associated protein-2 (MAP-2) transcripts. All three UTRs shared a common 171-bp sequence adjacent to the MAP-2 coding region and then diverged upstream. The size of the unique upstream sequence was 281, 146, or 104 bp. PCR of gen...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65041472.x
更新日期：1995-10-01 00:00:00
abstract：:Several Good buffers (MOPS, ACES, BES, HEPES, ADA, and PIPES) competitively inhibited both high-affinity and low-affinity [3H]gamma-aminobutyric acid receptor binding to rat brain synaptic membranes. The most potent inhibitor was MOPS, which had Ki values of 180 nM and 79 nM for the high- and low-affinity binding site...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1981.tb01708.x
更新日期：1981-03-01 00:00:00
abstract：:Quinolinic acid (QA) has been shown to evoke neurotoxic events via NMDA receptor (NMDAR) overactivation and oxidative stress. NMDARs are particularly vulnerable to free radicals, which can modulate protein tyrosine kinase (PTK) and phosphotyrosine phosphatase (PTP) activities. The src family of tyrosine kinases are as...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03814.x
更新日期：2006-06-01 00:00:00
abstract：:Axonal growth cone motility requires precise regulation of adhesion to navigate the complex environment of the nervous system and reach its target. Myristoylated alanine-rich C kinase substrate (MARCKS) protein is enriched in the developing brain and plays an important, phosphorylation-dependent role in the modulation...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13612
更新日期：2016-06-01 00:00:00
abstract：:Adult neurogenesis was first observed nearly 60 years ago, and it has since grown into an important neurochemistry research field. Much recent research has focused on the treatment of brain diseases through neuronal regeneration with endogenously generated neurons. In the adult brain, immature neurons called neuroblas...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.14002
更新日期：2017-06-01 00:00:00
abstract：:This laboratory has previously demonstrated that the mu-selective opiate receptor agonist sufentanil can produce a naloxone-reversible increase or decrease in the stimulated formation of cyclic AMP (cAMP) in the myenteric plexus, depending on the concentration of opioid used. On the basis of these results, it was sugg...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64031102.x
更新日期：1995-03-01 00:00:00
abstract：:Organotypic rat hippocampal slice cultures were used to study the role of excitatory amino acid transporters (EAATs) in kainate-induced cell death. Expression of the neuronal (EAAT3) or glial (EAAT2) transporters was inhibited with antisense phosphothioate oligonucleotides, and cytotoxicity was assessed with propidium...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：:Free radicals have been implicated in the etiology of many neurodegenerative conditions. Yet, because these species are highly reactive and thus short-lived it has been difficult to test these hypotheses. We adapted a method in which hydroxyl radicals are trapped by salicylate in vivo, resulting in the stable and quan...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64041819.x
更新日期：1995-04-01 00:00:00
abstract：:Brain-derived neurotrophic factor (BDNF) promotes the survival of various neuronal populations and thus shows potential in the treatment of neurodegenerative disease. However, BDNF is not pharmacokinetically optimal for use as a therapeutic agent. As a step toward the development of low-molecular-weight BDNF-like drug...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70041712.x
更新日期：1998-04-01 00:00:00
abstract：:An adrenomedullary protease capable of generating Met5-enkephalin from endogenous precursor(s) has been purified 1,000-fold using affinity chromatography in combination with gel filtration. This trypsin-like enzyme has an apparent molecular weight of 20,000 daltons by gel filtration. The reactivity of the enzyme towar...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb02802.x
更新日期：1984-05-01 00:00:00
abstract：:The interaction of triethyltin (TET) and trimethyltin (TMT) with rat brain astrocytes in vitro was investigated. Both compounds are highly neurotoxic after in vivo application, cause neurobehavioral changes, and elicit neuronal and glial responses in the CNS. In this study, 5-week-old cultures were exposed to TMT or T...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63062202.x
更新日期：1994-12-01 00:00:00
abstract：:Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD-1 gene product, ataxin-3. Ataxin-3 is degraded by the proteasome. However, the precise mechanism of ataxin-3 degradation remains to be elucidated. In this st...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04460.x
更新日期：2007-06-01 00:00:00
abstract：:The antisense strategy was used to unravel the functional contribution of the mRNAs encoding dopamine (DA) receptors to the multiple transduction mechanisms operated by DA in rat pituitary cells. An antisense oligonucleotide was designed to recognize seven nucleotides upstream and 11 nucleotides downstream from the in...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62041260.x
更新日期：1994-04-01 00:00:00
abstract：:beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) using biotin hydrazide and the coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide, under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated thr...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb13015.x
更新日期：1986-02-01 00:00:00
abstract：:The effects of muscarinic agonists and depolarizing agents on inositol phospholipid hydrolysis in the rabbit vagus nerve were assessed by the measurement of [3H]inositol monophosphate production in nerves that had been preincubated with [3H]inositol. After 1 h of drug action, carbachol, oxotremorine, and arecoline inc...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09392.x
更新日期：1992-08-01 00:00:00
abstract：:Using a cell culture model of the blood-brain barrier (BBB), we investigated the brain capillary endothelial cell (EC) response to hypoxia. The activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase and the GSH level of brain capillary ECs alone or i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65052138.x
更新日期：1995-11-01 00:00:00
abstract：:Carbonic anhydrase (CA) V is a mitochondrial enzyme that has been reported in several tissues of the gastrointestinal tract. In liver, it participates in ureagenesis and gluconeogenesis by providing bicarbonate ions for two other mitochondrial enzymes: carbamyl phosphate synthetase I and pyruvate carboxylase. This stu...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0752212.x
更新日期：2000-11-01 00:00:00
abstract：:Acetylcholine and choline release from rat brain synaptosomes have been measured using a chemiluminescent technique under a variety of conditions set up to mimic anoxic insult, including conditions of low pH (6.2) and the presence of lactate plus pyruvate as substrate. Lactate plus pyruvate as substrate consistently g...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb05658.x
更新日期：1987-04-01 00:00:00
abstract：:Caveolin-1 is the predominant structural protein of caveolae, a subset of (lipid) membrane rafts that compartmentalize cell signaling. Caveolin-1 binds most to G protein-coupled receptors and their signaling partners, thereby enhancing interactions among signaling cascade components and the relative activation of spec...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13852
更新日期：2016-12-01 00:00:00
abstract：:Discoidin domain receptor 1 (DDR1) is expressed in myelin oligodendrocytes and co-localizes with myelin basic protein (MBP). Alternative splicing of DDR1 generates five isoforms designated DDR1a-e. The MBP mRNA contains an hnRNP A2 response element (A2RE) sequence that is recognized by heterogeneous nuclear ribonucleo...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07580.x
更新日期：2012-02-01 00:00:00
abstract：:Most biological effects of tissue plasminogen activator (tPA), such as fibrinolysis, are mediated by its protease activity. Recent studies, however, have demonstrated that tPA also has several protease-independent effects such as: neuroprotection, microglial activation, and promoting LTP formation. In order to gain a ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04417.x
更新日期：2007-06-01 00:00:00
abstract：:In the present study, neuronal and Schwann cell marker proteins were used to biochemically characterize the spatiotemporal progress of degeneration/regeneration in the silicone chamber model for nerve regeneration. Rat sciatic nerves were transected and the proximal and distal stumps were inserted into a bridging sili...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb03260.x
更新日期：1993-03-01 00:00:00
abstract：:A loss of balance between excitatory and inhibitory signaling leads to excitoxicity, and contributes to ischemic cell death. Reduced synaptic inhibition as a result of dysfunction of the ionotropic GABAA receptor has been suggested as one of the major causes for this imbalance, although the underlying mechanisms remai...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02841.x
更新日期：2005-01-01 00:00:00
abstract：:Calcium/calmodulin-dependent kinase II (CaMKII) facilitates L-type calcium channel (LTCC) activity physiologically, but may exacerbate LTCC-dependent pathophysiology. We previously showed that CaMKII forms stable complexes with voltage-gated calcium channel (VGCC) beta(1b) or beta(2a) subunits, but not with the beta(3...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06436.x
更新日期：2010-01-01 00:00:00
abstract：:The protein kinase C γ (PKCγ) undergoes multistep activation and participates in various cellular processes in Purkinje cells. Perturbations in its phosphorylation state, conformation or localization can disrupt kinase signalling, such as in spinocerebellar ataxia type 14 (SCA14) that is caused by missense mutations i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12491
更新日期：2014-03-01 00:00:00
abstract：:We investigated the mechanism by which rat retina conserves docosahexaenoic acid during essential fatty acid deficiency. Weanling female albino rats were fed diets containing either 10% by weight hydrogenated coconut oil, safflower oil, or linseed oil for 15 weeks. Plasma and rod outer segment (ROS) membranes were pre...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb06369.x
更新日期：1991-11-01 00:00:00
abstract：:The activity-dependent fusion, retrieval and recycling of synaptic vesicles is essential for the maintenance of neurotransmission. Until relatively recently it was believed that most mutations in genes that were essential for this process would be incompatible with life, because of this fundamental role. However, an e...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.15035
更新日期：2020-05-07 00:00:00
abstract：:We recently described a new protein associated exclusively with neuronal clathrin-coated vesicles (CCVs), and characterized two monoclonal antibodies that react with it (S-8G8 and S-6G7). In this report, the association of neuronal protein of 185 kilodaltons (NP185) with CCV kinases and its interaction with tubulin ar...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb10929.x
更新日期：1989-01-01 00:00:00
