Biomedical subjects

S L Chan

Publications and source records attributed to S L Chan.

At least 37 records · Page 2Linked to original sources

PubMed2001

Evidence for a non-adrenoceptor, imidazoline-mediated contractile response to oxymetazoline in the porcine isolated rectal artery.

Imidazoline derivatives are known to elicit responses through both alpha(2)-adrenoceptor and non-adrenoceptor, imidazoline sites, though as yet there are no examples of the latter on vascular smooth muscle. In the presence of 0.3 microM prazosin, neither UK-14304 (0.01 - 3 microM) nor oxymetazoline (0.01 - 30 microM) caused a significant contraction of the porcine isolated rectal artery, a preparation with a low density of alpha(2)-adrenoceptors. In the presence of a combination of U46619 and forskolin, however, both agonists produced concentration-dependent contractions. Pretreatment with phenoxybenzamine (3 microM) abolished responses to UK-14304, but left those elicited by oxymetazoline largely unaffected. The putative I(3) imidazoline antagonist 2-(2,3 dihydro-2-benzofuranyl)-2-imidazole (KU-14R, 10 microM) caused a 6 fold rightward displacement of the phenoxybenzamine-insensitive concentration - response curve to oxymetazoline. Our data indicates that non-adrenoceptor, imidazoline sites, pharmacologically similar to the I(3) imidazoline site on islet cells, mediate vasoconstriction in the porcine isolated rectal artery.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2001

Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis of Alzheimer's disease.

Endoplasmic reticulum (ER) appears to be a focal point for alterations that result in neuronal dysfunction and death in Alzheimer's disease (AD). Aberrant proteolytic processing and/or trafficking of the beta-amyloid precursor protein (APP) in ER may promote neuronal degeneration by increasing the levels of the neurotoxic forms of beta-amyloid (A beta) and by decreasing the levels of the neuroprotective secreted form of APP (sAPP alpha). Some cases of AD are caused by mutations in the genes encoding presenilin 1 (PS1). When expressed in cultured neuronal cells and transgenic mice, PS1 mutations cause abnormalities in ER calcium homoeostasis, enhancing the calcium responses to stimuli that activate IP3- and ryanodine-sensitive ER calcium pools. Two major consequences of this disrupted ER calcium regulation are altered proteolytic processing of APP and increased vulnerability of neurons to apoptosis and excitotoxicity. The impact of PS1 mutations and aberrant APP processing is particularly great in synaptic terminals. Perturbed synaptic calcium homoeostasis promotes activation of apoptotic cascades involving production of Par-4 (prostate apoptosis response-4), mitochondrial dysfunction and caspase activation. A beta 42 (the 42-amino-acid form of A beta) induces membrane lipid peroxidation in synapses and dendrites resulting in impairment of membrane ion-motive ATPases and glucose and glutamate transporters. This disrupts synaptic ion and energy homoeostasis thereby promoting synaptic degeneration. In contrast, sAPP alpha activates signalling pathways that protect synapses against excitotoxicity and apoptosis. In the more common sporadic forms of AD, the initiating causes of the neurodegenerative cascade are less well defined, but probably involve increased levels of oxidative stress and impaired energy metabolism. Such alterations have been shown to disrupt neuronal calcium homoeostasis in experimental models, and may therefore feed into the same neurodegenerative cascade initiated by mutations in presenilins and APP. Perturbed synaptic ER calcium homoeostasis and consequent alterations in APP processing appear to be pivotal events in both sporadic and familial forms of AD.

Alzheimer Disease↗

PubMed2001

Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on N-methyl-D-aspartate channels.

Increased oxyradical production and membrane lipid peroxidation occur in neurons under physiological conditions and in neurodegenerative disorders. Lipid peroxidation can alter synaptic plasticity and may increase the vulnerability of neurons to excitotoxicity, but the underlying mechanisms are unknown. We report that 4-hydroxy-2,3-nonenal (4HN), an aldehyde product of lipid peroxidation, exerts a biphasic effect on NMDA-induced current in cultured rat hippocampal neurons with current being increased during the first 2 h and decreased after 6 h. Similarly, 4HN causes an early increase and a delayed decrease in NMDA-induced elevation of intracellular Ca2+ levels. In contrast, 4HN affects neither the ion current nor the Ca2+ response to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). The initial enhancement of NMDA-induced current is associated with increased phosphorylation of the NR1 receptor subunit, whereas the delayed suppression of current is associated with cellular ATP depletion and mitochondrial membrane depolarization. Cell death induced by 4HN is attenuated by an NMDA receptor antagonist, but not by an AMPA receptor antagonist. A secreted form of amyloid precursor protein, previously shown to protect neurons against oxidative and excitotoxic insults, prevented each of the effects of 4HN including the early and late changes in NMDA current, delayed ATP depletion, and cell death. These findings show that the membrane lipid peroxidation product 4HN can modulate NMDA channel activity, suggesting a role for this aldehyde in physiological and pathophysiological responses of neurons to oxidative stress.

Adenosine Triphosphate↗

PubMed2001

A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid beta-peptide.

The tumor suppressor protein p53 is essential for neuronal death in several experimental settings and may participate in human neurodegenerative disorders. Based upon recent studies characterizing chemical inhibitors of p53 in preclinical studies in the cancer therapy field, we synthesized the compound pifithrin-alpha and evaluated its potential neuroprotective properties in experimental models relevant to the pathogenesis of stroke and neurodegenerative disorders. Pifithrin-alpha protected neurons against apoptosis induced by DNA-damaging agents, amyloid beta-peptide and glutamate. Protection by pifithrin-alpha was correlated with decreased p53 DNA-binding activity, decreased expression of the p53 target gene BAX and suppression of mitochondrial dysfunction and caspase activation. Mice given pifithrin-alpha exhibited increased resistance of cortical and striatal neurons to focal ischemic injury and of hippocampal neurons to excitotoxic damage. These preclinical studies demonstrate the efficacy of a p53 inhibitor in models of stroke and neurodegenerative disorders, and suggest that drugs that inhibit p53 may reduce the extent of brain damage in related human neurodegenerative conditions.

Amyloid beta-Peptides↗

PubMed2001

Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits.

Calcium is one of the most important intracellular messengers in the brain, being essential for neuronal development, synaptic transmission and plasticity, and the regulation of various metabolic pathways. The findings reviewed in the present article suggest that calcium also plays a prominent role in the pathogenesis of Alzheimer's disease (AD). Associations between the pathological hallmarks ofAD (neurofibrillary tangles [NFT] and amyloid plaques) and perturbed cellular calcium homeostasis have been established in studies of patients, and in animal and cell culture models of AD. Studies of the effects of mutations in the beta-amyloid precursor protein (APP) and presenilins on neuronal plasticity and survival have provided insight into the molecular cascades that result in synaptic dysfunction and neuronal degeneration in AD. Central to the neurodegenerative process is the inability of neurons to properly regulate intracellular calcium levels. Increased levels of amyloid beta-peptide (Abeta) induce oxidative stress, which impairs cellular ion homeostasis and energy metabolism and renders neurons vulnerable to apoptosis and excitotoxicity. Subtoxic levels of Abeta may induce synaptic dysfunction by impairing multiple signal transduction pathways. Presenilin mutations perturb calcium homeostasis in the endoplasmic reticulum in a way that sensitizes neurons to apoptosis and excitotoxicity; links between aberrant calcium regulation and altered APP processing are emerging. Environmental risk factors for AD are being identified and may include high calorie diets, folic acid insufficiency, and a low level of intellectual activity (bad habits); in each case, the environmental factor impacts on neuronal calcium homeostasis. Low calorie diets and intellectual activity may guard against AD by stimulating production of neurotrophic factors and chaperone proteins. The emerging picture of the cell and molecular biology of AD is revealing novel preventative and therapeutic strategies for eradicating this growing epidemic of the elderly.

Alzheimer Disease↗

PubMed2001

Imidazoline binding sites in the endocrine pancreas: can they fulfil their potential as targets for the development of new insulin secretagogues?

A variety of compounds containing an imidazoline ring have the ability to stimulate insulin secretion. Many of these also improve glycaemia in experimental models of type 2 diabetes and in man, suggesting that this class may be useful in the development of new orally active anti-diabetic drugs. However, the mechanisms by which imidazolines promote insulin secretion have not been clarified. The response does not appear to be due to the binding of ligands to either of the two major types of "imidazoline receptor" defined by pharmacological criteria (I1 and I2 sites) but may result from interaction with a novel imidazoline binding site. One such site has been identified in association with the ATP-sensitive potassium (K(ATP)) channel in the beta-cell and has been designated "I3". Electrophysiological and biochemical evidence suggest that the I3 site may be intrinsic to the ion-conducting pore component, Kir6.2, of the K(ATP) channel, but the effects of imidazoline ligands on insulin secretion can be dissociated from the regulation of Kir6.2. Indeed, there is increasing evidence that some imidazolines can control exocytosis directly, both in beta-cells and in pancreatic alpha-cells. Thus, it is proposed that a further imidazoline binding site is primarily responsible for control of hormone secretion. Evidence is reviewed which suggests that this site occupies a central position within an amplification pathway that also mediates the effects of cAMP in the beta-cell. Characterisation of this site should provide the stimulus for the design of new insulin secretagogues that are devoid of K(ATP) channel-blocking properties.

Animals↗

PubMed2001

Characterization of a KATP channel-independent pathway involved in potentiation of insulin secretion by efaroxan.

Efaroxan, like several other imidazoline reagents, elicits a glucose-dependent increase in insulin secretion from pancreatic beta-cells. This response has been attributed to efaroxan-mediated blockade of KATP channels, with the subsequent gating of voltage-sensitive calcium channels. However, increasing evidence suggests that, at best, this mechanism can account for only part of the secretory response to the imidazoline. In support of this, we now show that efaroxan can induce functional changes in the secretory pathway of pancreatic beta-cells that are independent of KATP channel blockade. In particular, efaroxan was found to promote a sustained sensitization of glucose-induced insulin release that persisted after removal of the drug and to potentiate Ca2+-induced insulin secretion from electropermeabilized islets. To investigate the mechanisms involved, we studied the effects of the efaroxan antagonist KU14R. This agent is known to selectively inhibit insulin secretion induced by efaroxan, without altering the secretory response to glucose or KCl. Surprisingly, however, KU14R markedly impaired the potentiation of insulin secretion mediated by agents that raise cAMP, including the adenylate cyclase activator, forskolin, and the phosphodiesterase inhibitor isobutylmethyl xanthine (IBMX). These effects were not accompanied by any reduction in cAMP levels, suggesting an antagonistic action of KU14R at a more distal point in the pathway of potentiation. In accord with our previous work, islets that were exposed to efaroxan for 24 h became selectively desensitized to this agent, but they still responded normally to glucose. Unexpectedly, however, the ability of either forskolin or IBMX to potentiate glucose-induced insulin secretion was severely impaired in these islets. By contrast, the elevation of cAMP was unaffected by culture of islets with efaroxan. Taken together, the data suggest that, in addition to effects on the KATP channel, imidazolines also interact with a more distal component that is crucial to the potentiation of insulin secretion. This component is not required for Ca2+-dependent secretion per se but is essential to the mechanism by which cAMP potentiates insulin release. Overall, the results indicate that the actions of efaroxan at this distal site may be more important for control of insulin secretion than its effects on the KATP channel.

1-Methyl-3-isobutylxanthine↗

PubMed2001

Efficacy of the BCG revaccination programme in a cohort given BCG vaccination at birth in Hong Kong.

SETTING: Revaccination of tuberculin-negative school-children is a regular practice in Hong Kong. OBJECTIVE: To assess the efficacy of BCG revaccination guided by tuberculin skin testing. METHOD: A cohort of 303,692 children vaccinated at birth was followed through the tuberculosis notification register for the development of active disease. The percentage of cohort who participated in the BCG revaccination program during primary school was estimated from the vaccination statistics of the Hong Kong Department of Health. The BCG revaccination history of identified cases was ascertained through vaccination cards and clinic records. RESULTS: A total of 85.2% of the cohort participated in the BCG revaccination programme; 79.7% of the participants were tuberculin-negative and revaccinated; 343 developed tuberculosis after the age of 11; 302 were among the participants in the programme while 41 were not. The tuberculosis incidence was 16.5 and 12.9 per 100,000 person-years for participants and non-participants, respectively (RR 1.28, 95%CI 0.92-1.77). Among the participants, tuberculosis incidence was 12.5 and 32.0/100,000 person-years, respectively, for the tuberculin-negative/BCG revaccinated group and the tuberculin-positive/non-revaccinated group (RR 0.39, 95%CI 0.31-0.49). CONCLUSION: This study failed to demonstrate any significant difference in the incidence rates of tuberculosis among participants and non-participants in a school BCG revaccination programme. The increased risk for tuberculosis in the tuberculin-positive group does not support the use of the tuberculin testing for detection of immunity conferred by neonatal BCG vaccination.

Adolescent↗

PubMed2001

A young male patient with persistent fever due to tuberculous peritonitis.

Tuberculous peritonitis is an uncommon disease in Hong Kong. We report a case of tuberculous peritonitis in a young male. The patient presented with persistent fever and intermittent cough for 1 month, but had no gastrointestinal symptoms. It was only through detection of slight abdominal ascites that subsequent abdominal paracentesis and laparoscopic biopsy confirmed the diagnosis. Appropriate antituberculous treatment was prescribed. Progress was complicated by persistent fever and liver function derangement, successfully managed by careful titration of antituberculous medications.

Adult↗

PubMed2000

MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains.

A novel Bax-associating protein, named MAP-1 (Modulator of Apoptosis), has been identified in a yeast two-hybrid screen. MAP-1 contains a BH3-like (BH: Bcl-2 homology) motif and mediates caspase-dependent apoptosis in mammalian cells when overexpressed. MAP-1 homodimerizes and associates with the proapoptotic Bax and the prosurvival Bcl-2 and Bcl-X(L) of the Bcl-2 family in vitro and in vivo in mammalian cells. Mutagenesis analyses revealed that the BH3-like domain in MAP-1 is not required for its association with Bcl-X(L) but is required for association with Bax and for mediating apoptosis. Interestingly, in contrast to other Bax-associating proteins such as Bcl-X(L) and Bid, which require the BH3 and BH1 domains of Bax, respectively, for binding, the binding of MAP-1 to Bax appears to require all three BH domains (BH1, BH2, and BH3) of Bax, because point mutation of the critical amino acid in any one of these domains is sufficient to abolish its binding to MAP-1. These data suggest that MAP-1 mediates apoptosis through a mechanism that involves binding to Bax.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity.

Elevated plasma levels of the sulfur-containing amino acid homocysteine increase the risk for atherosclerosis, stroke, and possibly Alzheimer's disease, but the underlying mechanisms are unknown. We now report that homocysteine induces apoptosis in rat hippocampal neurons. DNA strand breaks and associated activation of poly-ADP-ribose polymerase (PARP) and NAD depletion occur rapidly after exposure to homocysteine and precede mitochondrial dysfunction, oxidative stress, and caspase activation. The PARP inhibitor 3-aminobenzamide (3AB) protects neurons against homocysteine-induced NAD depletion, loss of mitochondrial transmembrane potential, and cell death, demonstrating a requirement for PARP activation and/or NAD depletion in homocysteine-induced apoptosis. Caspase inhibition accelerates the loss of mitochondrial potential and shifts the mode of cell death to necrosis; inhibition of PARP with 3AB attenuates this effect of caspase inhibition. Homocysteine markedly increases the vulnerability of hippocampal neurons to excitotoxic and oxidative injury in cell culture and in vivo, suggesting a mechanism by which homocysteine may contribute to the pathogenesis of neurodegenerative disorders.

Animals↗

PubMed2000

The Caenorhabditis elegans sex determination protein FEM-1 is a CED-3 substrate that associates with CED-4 and mediates apoptosis in mammalian cells.

Sex-specific elimination of cells by apoptosis plays a role in sex determination in Caenorhabditis elegans. Recently, a mammalian pro-apoptotic protein named F1Aalpha has been identified. F1Aalpha shares extensive homology throughout the entire protein with the C. elegans protein, FEM-1, which is essential for achieving all aspects of the male phenotype in the nematode. In this report, the role of FEM-1 in apoptosis was investigated. Overexpression of FEM-1 induces caspase-dependent apoptosis in mammalian cells. FEM-1 is cleaved in vitro by the C. elegans caspase, CED-3, generating an N-terminal cleavage product that corresponds to the minimal effector domain for apoptosis. Furthermore, CED-4 associates with FEM-1 in vitro and in vivo in mammalian cells and potentiates FEM-1-mediated apoptosis. Similarly, Apaf-1, the mammalian homologue of CED-4 was found to associate with F1Aalpha. These data suggest that FEM-1 and F1Aalpha may mediate apoptosis by communicating directly with the core machinery of apoptosis.

Animals↗

PubMed2000

Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons.

Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. PS1 mutations may perturb cellular Ca(2+) homeostasis and thereby render neurons vulnerable to excitotoxicity and apoptosis. We now report that PC12 cells expressing PS1 mutations and primary hippocampal neurons from PS1 mutant knockin mice exhibit greatly increased levels of ryanodine receptors (RyR) and enhanced Ca(2+) release following stimulation with caffeine. Double-labeling immunostaining and co-immunoprecipitation analyses indicate that PS1 and RyR are colocalized and interact physically. Caffeine treatment sensitizes neurons expressing mutant PS1 to apoptosis induced by amyloid beta-peptide, a neurotic peptide linked to the pathogenesis of AD. When taken together with recent evidence for alterations in RyR in brains of AD patients, our data suggest that PS1 mutations may promote neuronal degeneration in AD by increasing transcription and translation of RyR and altering functional properties of ryanodine-sensitive Ca(2+) pools.

Animals↗

PubMed2000

Caspase-mediated degradation of AMPA receptor subunits: a mechanism for preventing excitotoxic necrosis and ensuring apoptosis.

Activation of ionotropic glutamate receptors of the AMPA and NMDA subtypes likely contributes to neuronal injury and death in various neurodegenerative disorders. Excitotoxicity can manifest as either apoptosis or necrosis, but the mechanisms that determine the mode of cell death are not known. We now report that levels of AMPA receptor subunits GluR-1 and GluR-4 are rapidly decreased in cultured rat hippocampal neurons undergoing apoptosis in response to withdrawal of trophic support (WTS), whereas levels of NMDA receptor subunits NR1, NR2A, and NR2B are unchanged. Exposure of isolated synaptosomal membranes to "apoptotic" cytosolic extracts resulted in rapid degradation of AMPA receptor subunits. Treatment of cells and synaptosomal membranes with the caspase inhibitors prevented degradation of AMPA receptor subunits, demonstrating a requirement for caspases in the process. Calcium responses to AMPA receptor activation were reduced after withdrawal of trophic support and enhanced after treatment with caspase inhibitors. Vulnerability of neurons to excitotoxic necrosis was decreased after withdrawal of trophic support and potentiated by treatment with caspase inhibitors. Our data indicate that caspase-mediated degradation of AMPA receptor subunits occurs during early periods of cell stress and may serve to ensure apoptosis by preventing excitotoxic necrosis.

Amino Acid Chloromethyl Ketones↗

PubMed2000

Concentration- and cell type-specific effects of calbindin D28k on vulnerability of hippocampal neurons to seizure-induced injury.

The calcium-binding protein calbindin D28k (CB) is expressed in limited subpopulations of neurons in the brain. In the hippocampus, CB is expressed in all dentate granule cells and a subpopulation of CA1 pyramidal neurons, but is absent from CA3 neurons. This pattern of CB expression is inversely correlated with neuronal vulnerability to seizure-induced damage suggesting the possibility that expression of CB confers resistance to excitotoxicity. While data from cell culture studies support an excitoprotective role for calbindin, it is not known whether CB is a key determinant of neuronal vulnerability in vivo. We therefore examined the pattern of damage to hippocampal neurons following intrahippocampal injection of the seizure-inducing excitotoxin kainate in CB homozygous (CB-/-) and CB heterozygous (CB+/-) knockout mice in comparison with wild-type mice (CB+/+). Whereas the extent of damage to CA1 neurons was similar in CB-/- and CB+/+ mice, damage to CA1 neurons was significantly reduced in CB+/- mice. Dentate granule neurons were not damaged following kainate-induced seizures in CB+/+, CB+/- or CB-/- mice. These findings suggest that CB can modify vulnerability of hippocampal CA1 neurons to seizure-induced injury, and that either CB is not a critical determinant of resistance of dentate granule neurons, or compensatory changes occur and lack of CB is not the only difference between CB-/- and CB+/+ mice.

Animals↗

PubMed2000

Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders.

Endoplasmic reticulum (ER) is a multifaceted organelle that regulates protein synthesis and trafficking, cellular responses to stress, and intracellular Ca2+ levels. In neurons, it is distributed between the cellular compartments that regulate plasticity and survival, which include axons, dendrites, growth cones and synaptic terminals. Intriguing communication networks between ER, mitochondria and plasma membrane are being revealed that provide mechanisms for the precise regulation of temporal and spatial aspects of Ca2+ signaling. Alterations in Ca2+ homeostasis in ER contribute to neuronal apoptosis and excitotoxicity, and are being linked to the pathogenesis of several different neurodegenerative disorders, including Alzheimer's disease and stroke.

Animals↗

PubMed2000

The rat ortholog of the presumptive flounder antifreeze enhancer-binding protein is a helicase domain-containing protein.

The expression of winter flounder liver-type antifreeze protein (wflAFP) genes is tissue-specific and under seasonal and hormonal regulation. The only intron of the major wflAFP gene was demonstrated to be a liver-specific enhancer in both mammalian cell lines and flounder hepatocytes. Element B, the core enhancer sequence, was shown to interact specifically with a liver-enriched transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPalpha), as well as a presumptive antifreeze enhancer-binding protein (AEP). In this study, the identity of the rat AEP ortholog was revealed via its DNA-protein interaction with element B. It is a helicase-domain-containing protein, 988 amino acids in length, and is homologous to mouse Smubp-2, hamster Rip-1 and human Smubp-2. The specific binding between element B and AEP was confirmed by South-Western analysis and gel retardation assays. Residues in element B important to this interaction were identified by methylation interference assays. Mutation on one of the residues disrupted the binding between element B and AEP and its enhancer activity was significantly reduced, suggesting that AEP is essential for the transactivation of the wflAFP gene intron. The rat AEP is ubiquitously expressed in various tissues, and the flounder homolog is present as shown by genomic Southern analysis. The potential role of AEP in regulating the flounder AFP gene expression is discussed.

Amino Acid Sequence↗

PubMed2000

A mechanism for the neuroprotective effect of apolipoprotein E: isoform-specific modification by the lipid peroxidation product 4-hydroxynonenal.

Inheritance of the apolipoprotein E (apoE) epsilon4 allele increases the risk for Alzheimer's disease and may also influence the pathogenesis of other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). The influence of apoE genotype on disease susceptibility must ultimately be explained by the fact that apoE proteins differ in only two amino acids: apoE2 has two cysteine residues, apoE3 has one cysteine residue, and apoE4 has none. We previously reported increased protein modification by the lipid peroxidation product 4-hydroxynonenal (HNE), which covalently binds to proteins on cysteine residues, in human ALS lumbar spinal cord. We now report increased levels of HNE-modified apoE in lumbar spinal cord samples from mice expressing an ALS-linked mutation in Cu/Zn-superoxide dismutase relative to controls. Studies of interactions of pure apoE proteins with HNE showed that the isoforms differ in the amount of HNE they can bind, with the order E2 > E3 > E4. This correlated with the differential ability of apoE isoforms to protect against apoptosis induced by HNE in cultures of mouse spinal cord motor neurons and by the amyloid beta-peptide in cultures of rat hippocampal neurons. These data suggest that apoE plays a major role in detoxifying HNE, and the differential neuroprotective effect of its isoforms may help explain the relationship between apoE genotype and the susceptibility to neurodegenerative diseases.

Aldehydes↗