Todd E. Golde

Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains.

A presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and notch.

A physiologic signaling role for the gamma -secretase-derived intracellular fragment of APP.

FAD-linked mutations in presenilin 1 alter the length of Abeta peptides derived from betaAPP transmembrane domain mutants.

Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle.

Identification of a novel family of presenilin homologues.

Inflammation takes on Alzheimer disease.

Open peer commentary regarding Abeta immunization and CNS inflammation by Pasinetti et al.

Alzheimer disease therapy: can the amyloid cascade be halted?

Physiologic and pathologic events mediated by intramembranous and juxtamembranous proteolysis.

Overexpression of nicastrin increases Abeta production.

Peptide-based, irreversible inhibitors of gamma-secretase activity.

Abeta42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) and ErbB-4 receptor and signaling through the APP intracellular domain.

The non-cyclooxygenase targets of non-steroidal anti-inflammatory drugs, lipoxygenases, peroxisome proliferator-activated receptor, inhibitor of kappa B kinase, and NF kappa B, do not reduce amyloid beta 42 production.

Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity.

Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction.

NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo.

Immune responses against Abeta1-42 in HLA class II transgenic mice: implications for Abeta1-42 immune-mediated therapies.

TCR-mediated Notch signaling regulates proliferation and IFN-gamma production in peripheral T cells.

Intramembrane-cleaving aspartic proteases and disease: presenilins, signal peptide peptidase and their homologs.

Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma-/- knock-out mice.

Signal peptide peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor.

A signal peptide peptidase (SPP) reporter activity assay based on the cleavage of type II membrane protein substrates provides further evidence for an inverted orientation of the SPP active site relative to presenilin.

Presenilin regulates capacitative calcium entry dependently and independently of gamma-secretase activity.

Homing in on intracellular Abeta?

The Abeta hypothesis: leading us to rationally-designed therapeutic strategies for the treatment or prevention of Alzheimer disease.

Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production.

Bringing amyloid into focus.

Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells.

Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21.

Inhibitors of Rho-kinase modulate amyloid-beta (Abeta) secretion but lack selectivity for Abeta42.

C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation.

Notch1 augments NF-kappaB activity by facilitating its nuclear retention.

Efficient neuronal gene transfer with AAV8 leads to neurotoxic levels of tau or green fluorescent proteins.

Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model.

Detection of presenilin-1 homodimer formation in intact cells using fluorescent lifetime imaging microscopy.

Inclusion-body myositis and Alzheimer disease: two sides of the same coin, or different currencies altogether?

Signal peptide peptidase: biochemical properties and modulation by nonsteroidal antiinflammatory drugs.

Interleukin-1 receptor 1 knockout has no effect on amyloid deposition in Tg2576 mice and does not alter efficacy following Abeta immunotherapy.

Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase.

Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel gamma-secretase substrates.

Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer's disease mouse models.

Disease modifying therapy for AD?

Signal peptide peptidase (SPP) dimer formation as assessed by fluorescence lifetime imaging microscopy (FLIM) in intact cells.

Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice.

Filling the gaps in the abeta cascade hypothesis of Alzheimer's disease.

The pathogenesis of Alzheimer's disease and the role of Abeta42.

Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Abeta levels.

Notch inhibition in Kaposi's sarcoma tumor cells leads to mitotic catastrophe through nuclear factor-kappaB signaling.

Statins reduce amyloid-beta production through inhibition of protein isoprenylation.

Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice.

Epidermal growth factor receptor and notch pathways participate in the tumor suppressor function of gamma-secretase.

Off the beaten pathway: the complex cross talk between Notch and NF-kappaB.

Notch signaling is activated by TLR stimulation and regulates macrophage functions.

Safety, tolerability, pharmacokinetics, and Abeta levels after short-term administration of R-flurbiprofen in healthy elderly individuals.

Possible mechanisms of action of NSAIDs and related compounds that modulate gamma-secretase cleavage.

Independent generation of Abeta42 and Abeta38 peptide species by gamma-secretase.

Using leucine zipper to facilitate alpha-synuclein assembly.

BRI2 (ITM2b) inhibits Abeta deposition in vivo.

Substrate-targeting gamma-secretase modulators.

Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells.

Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases.

"What kills neurons in neurodegenerative diseases?", a review series in an open access journal.

The therapeutic importance of understanding mechanisms of neuronal cell death in neurodegenerative disease.

Notch regulates cytolytic effector function in CD8+ T cells.

Quantitative and mechanistic studies of Abeta immunotherapy.

Identification of ligand-induced proteolytic cleavage and ectodomain shedding of VEGFR-1/FLT1 in leukemic cancer cells.

Inhibition of soluble TNF signaling in a mouse model of Alzheimer's disease prevents pre-plaque amyloid-associated neuropathology.

A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.

Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity.

Medicine. Avoiding unintended toxicity.

Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575.

Signal peptide peptidases: a family of intramembrane-cleaving proteases that cleave type 2 transmembrane proteins.

Generating differentially targeted amyloid-beta specific intrabodies as a passive vaccination strategy for Alzheimer's disease.

Targeting Abeta and tau in Alzheimer's disease, an early interim report.

Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia.

An NSAID-like compound, FT-9, preferentially inhibits gamma-secretase cleavage of the amyloid precursor protein compared to its effect on amyloid precursor-like protein 1.

Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer's and other neurodegenerative diseases.

Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition.

IFN-gamma promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice.

Convection-enhanced delivery and systemic mannitol increase gene product distribution of AAV vectors 5, 8, and 9 and increase gene product in the adult mouse brain.

Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation.

Phosphorylation dynamics regulate Hsp27-mediated rescue of neuronal plasticity deficits in tau transgenic mice.

Sorting out frontotemporal dementia?

Reduced Alzheimer's disease ß-amyloid deposition in transgenic mice expressing S-palmitoylation-deficient APH1aL and nicastrin.

Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift.

Hippocampal expression of murine TNFα results in attenuation of amyloid deposition in vivo.

Robust amyloid clearance in a mouse model of Alzheimer's disease provides novel insights into the mechanism of amyloid-beta immunotherapy.

Right sizing funding for Alzheimer's disease.

Interferon-γ induces progressive nigrostriatal degeneration and basal ganglia calcification.

Lysine 624 of the amyloid precursor protein (APP) is a critical determinant of amyloid β peptide length: support for a sequential model of γ-secretase intramembrane proteolysis and regulation by the amyloid β precursor protein (APP) juxtamembrane region.

Substrate sequence influences γ-secretase modulator activity, role of the transmembrane domain of the amyloid precursor protein.

Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and Aβ oligomerization.

Adeno-associated virus-mediated brain delivery of 5-lipoxygenase modulates the AD-like phenotype of APP mice.

Shifting a complex debate on γ-secretase cleavage and Alzheimer's disease.

Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains.

Hippocampal expression of murine IL-4 results in exacerbation of amyloid deposition.

Transient pharmacologic lowering of Aβ production prior to deposition results in sustained reduction of amyloid plaque pathology.

Alzheimer's β-secretase (BACE1) regulates the cAMP/PKA/CREB pathway independently of β-amyloid.

Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo.

5-Lipoxygenase gene transfer worsens memory, amyloid, and tau brain pathologies in a mouse model of Alzheimer disease.

Retention in endoplasmic reticulum 1 (RER1) modulates amyloid-β (Aβ) production by altering trafficking of γ-secretase and amyloid precursor protein (APP).

Cyanobacterial peptides as a prototype for the design of potent β-secretase inhibitors and the development of selective chemical probes for other aspartic proteases.

Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design.

Analysis of proteolytic processes and enzymatic activities in the generation of huntingtin n-terminal fragments in an HEK293 cell model.

Viral transduction of the neonatal brain delivers controllable genetic mosaicism for visualising and manipulating neuronal circuits in vivo.

Reversible pathologic and cognitive phenotypes in an inducible model of Alzheimer-amyloidosis.

Biomarkers for Alzheimer's disease in plasma, serum and blood - conceptual and practical problems.

Thinking laterally about neurodegenerative proteinopathies.

Robust cytoplasmic accumulation of phosphorylated TDP-43 in transgenic models of tauopathy.

Alzheimer's disease risk alleles in TREM2 illuminate innate immunity in Alzheimer's disease.

Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models".

Conformational templating of α-synuclein aggregates in neuronal-glial cultures.

Steroids as γ-secretase modulators.

Progress in Alzheimer's disease research circa 2013: Is the glass half empty or half full?

Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia.

Unbiased screen reveals ubiquilin-1 and -2 highly associated with huntingtin inclusions.

γ-Secretase inhibitors and modulators.

Capsid serotype and timing of injection determines AAV transduction in the neonatal mice brain.

Accelerated neurodegeneration through chaperone-mediated oligomerization of tau.

Anti-tau antibodies: hitting the target.

Induction of CNS α-synuclein pathology by fibrillar and non-amyloidogenic recombinant α-synuclein.

γ-Secretase processing and effects of γ-secretase inhibitors and modulators on long Aβ peptides in cells.

Open questions for Alzheimer's disease immunotherapy.

Non-Canonical Notch Signaling Drives Activation and Differentiation of Peripheral CD4(+) T Cells.

Complex relationships between substrate sequence and sensitivity to alterations in γ-secretase processivity induced by γ-secretase modulators.

Genetic suppression of transgenic APP rescues Hypersynchronous network activity in a mouse model of Alzeimer's disease.

Amyloidogenic α-synuclein seeds do not invariably induce rapid, widespread pathology in mice.

NOTCH1 Can Initiate NF-κB Activation via Cytosolic Interactions with Components of the T Cell Signalosome.

Divergent effects of the H50Q and G51D SNCA mutations on the aggregation of α-synuclein.

Intramuscular injection of α-synuclein induces CNS α-synuclein pathology and a rapid-onset motor phenotype in transgenic mice.

Brain Injection of α-Synuclein Induces Multiple Proteinopathies, Gliosis, and a Neuronal Injury Marker.