Taking Advantage of the Selectivity of Histone Deacetylases and Phosphodiesterase Inhibitors to Design Better Therapeutic Strategies to Treat Alzheimer’s Disease

Evaluation of the efficacy, safety and tolerability of orally administered BI 409306, a novel phosphodiesterase type 9 inhibitor, in two randomised controlled phase II studies in patients with prodromal and mild Alzheimer’s disease

(2019) Lutz Frölich et al.   Alzheimers Research & Therapy

Histone Deacetylase Inhibitors as Multitarget Ligands: New Players in Alzheimer's Disease Drug Discovery?

(2019) Angela De Simone et al.   ChemMedChem

Design, synthesis, biological evaluation and in vivo testing of dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors for the treatment of Alzheimer's disease

(2018) Obdulia Rabal et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Tubastatin A/ACY-1215 Improves Cognition in Alzheimer's Disease Transgenic Mice

(2018) Ling Zhang et al.   JOURNAL OF ALZHEIMERS DISEASE

HDAC2 dysregulation in the nucleus basalis of Meynert during the progression of Alzheimer's disease

(2018) Laura Mahady et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Discovery of in Vivo Chemical Probes for Treating Alzheimer’s Disease: Dual Phosphodiesterase 5 (PDE5) and Class I Histone Deacetylase Selective Inhibitors

(2018) Obdulia Rabal et al.   ACS Chemical Neuroscience

CoREST Complex-Selective Histone Deacetylase Inhibitors Show Prosynaptic Effects and an Improved Safety Profile To Enable Treatment of Synaptopathies

(2018) Nathan O. Fuller et al.   ACS Chemical Neuroscience

Histone Deacetylase 2 Inhibition Attenuates Downregulation of Hippocampal Plasticity Gene Expression during Aging

(2017) Padmanabh Singh et al.   MOLECULAR NEUROBIOLOGY

Inducing heat shock protein 70 expression provides a robust anti-thrombotic effect with minimal bleeding risk

(2017) Mikel Allende et al.   THROMBOSIS AND HAEMOSTASIS

HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients

(2017) Wenting Guo et al.   Nature Communications

The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer’s disease

(2017) Shuang-shuang Yang et al.   Translational Neurodegeneration

Impact of Scaffold Exploration on Novel Dual-Acting Histone Deacetylases and Phosphodiesterase 5 Inhibitors for the Treatment of Alzheimer’s Disease

(2016) Juan A. Sánchez-Arias et al.   ACS Chemical Neuroscience

Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer’s Disease

(2016) Obdulia Rabal et al.   JOURNAL OF MEDICINAL CHEMISTRY

A First-in-Class Small-Molecule that Acts as a Dual Inhibitor of HDAC and PDE5 and that Rescues Hippocampal Synaptic Impairment in Alzheimer’s Disease Mice

(2016) Mar Cuadrado-Tejedor et al.   NEUROPSYCHOPHARMACOLOGY

Linking HSP90 target occupancy to HSP70 induction and efficacy in mouse brain

(2016) Kenneth Thirstrup et al.   PHARMACOLOGICAL RESEARCH

Selective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1-42-mediated cytotoxicity

(2016) Ryan T. Cameron et al.   FEBS Open Bio

Decreased levels of guanosine 3′, 5′-monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease

(2015) Ana Ugarte et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Pharmacological Selectivity Within Class I Histone Deacetylases Predicts Effects on Synaptic Function and Memory Rescue

(2015) Gavin Rumbaugh et al.   NEUROPSYCHOPHARMACOLOGY

Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer’s disease

(2015) M. Cuadrado-Tejedor et al.   Clinical Epigenetics

A Multicenter, Double-Blind, Placebo-Controlled Trial of the PDE9A Inhibitor, PF-04447943, in Alzheimer’s Disease

(2014) Elias Schwam et al.   Current Alzheimer Research

Phosphodiesterase 9: Insights from protein structure and role in therapeutics

(2014) Nivedita Singh et al.   LIFE SCIENCES

Alzheimer’s disease drug-development pipeline: few candidates, frequent failures

(2014) Jeffrey L Cummings et al.   Alzheimers Research & Therapy

Heat Shock Proteins at the Crossroads between Cancer and Alzheimer’s Disease

(2014) Hao Wang et al.   Biomed Research International

Phosphodiesterases as Therapeutic Targets for Alzheimer's Disease

(2012) Ana García-Osta et al.   ACS Chemical Neuroscience

Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease

(2012) You Me Sung et al.   EXPERIMENTAL NEUROLOGY

Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation

(2012) Casey Cook et al.   HUMAN MOLECULAR GENETICS

HDAC6 Inhibitor Blocks Amyloid Beta-Induced Impairment of Mitochondrial Transport in Hippocampal Neurons

(2012) Chaeyoung Kim et al.   PLoS One

Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease

(2010) Ana Ricobaraza et al.   HIPPOCAMPUS

HDAC2 negatively regulates memory formation and synaptic plasticity

(2009) Ji-Song Guan et al.   NATURE

Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats

(2008) Stephen Maren   EUROPEAN JOURNAL OF NEUROSCIENCE

Histone deacetylase 6 interacts with the microtubule-associated protein tau

(2008) Huiping Ding et al.   JOURNAL OF NEUROCHEMISTRY