Philip Wing‐Lok Ho
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View article: Affective phenotypes in heterozygous LRRK2 R1441G knock-in mice
Affective phenotypes in heterozygous LRRK2 R1441G knock-in mice Open
Several missense mutations in the LRRK2 gene are linked to familial Parkinson’s disease (PD). Although LRRK2 mutant mouse models typically lack gross motor impairments, their contribution to non-motor PD symptoms remains largely underexplo…
View article: Long-term oral regimen of glucocerebrosidase activator reduces a-synuclein oligomer accumulation in aged LRRK2 mutant mouse brains - therapeutic implication of Parkinson’s disease
Long-term oral regimen of glucocerebrosidase activator reduces a-synuclein oligomer accumulation in aged LRRK2 mutant mouse brains - therapeutic implication of Parkinson’s disease Open
Deposition of misfolded a-synuclein (a-syn) aggregates in brain is a pathological hallmark of Parkinson’s disease (PD). Accumulation of toxic soluble a-syn seeds in patient cerebrospinal fluid represents a prodromal marker of synucleinopat…
View article: The changes in global burden of autoimmune diseases two years after the COVID-19 pandemic: a trend analysis based on the Global Burden of Disease Study 2021
The changes in global burden of autoimmune diseases two years after the COVID-19 pandemic: a trend analysis based on the Global Burden of Disease Study 2021 Open
The year 2019 marked a pivotal point for increased global burden of PsO and regional burdens of other ADs. These observations have important implications for subsequent healthcare planning and resource allocation.
View article: Effects of Meditation and Yoga on Anxiety, Depression and Chronic Inflammation in Patients with Parkinson’s Disease: A Randomized Clinical Trial
Effects of Meditation and Yoga on Anxiety, Depression and Chronic Inflammation in Patients with Parkinson’s Disease: A Randomized Clinical Trial Open
Introduction: Clinical guidelines recommend a holistic approach to Parkinson’s disease (PD) care, yet randomized trials examining mindfulness-based interventions in this context are scarce. This study investigated the effects of two mindfu…
View article: Rare Variants May Influence Disease Risk and Clinical Features in Sporadic Late-Onset Chinese Parkinson's Disease Patients
Rare Variants May Influence Disease Risk and Clinical Features in Sporadic Late-Onset Chinese Parkinson's Disease Patients Open
View article: Myasthenia gravis following statin therapy: evidence from target trial emulation and self-controlled case series study
Myasthenia gravis following statin therapy: evidence from target trial emulation and self-controlled case series study Open
Several international pharmacovigilance agencies have issued warnings regarding the potential risk of myasthenia gravis (MG) following statin therapy. Our study investigated this association using population-based electronic health records…
View article: Loss of mitochondrial Ca2+ response and CaMKII/ERK activation by LRRK2R1441G mutation correlate with impaired depolarization-induced mitophagy
Loss of mitochondrial Ca2+ response and CaMKII/ERK activation by LRRK2R1441G mutation correlate with impaired depolarization-induced mitophagy Open
Pathogenic LRRK2R1441G mutation abolished mitochondrial depolarization-induced Ca2+ response and impaired the basal mitochondrial clearance. Inherent defects from LRRK2 mutation have weakened the cellular ability to s…
View article: A randomized controlled trial on the effects and acceptability of individual mindfulness techniques – meditation and yoga – on anxiety and depression in people with Parkinson’s disease: a study protocol
A randomized controlled trial on the effects and acceptability of individual mindfulness techniques – meditation and yoga – on anxiety and depression in people with Parkinson’s disease: a study protocol Open
Background Between 40 and 50% of patients with Parkinson’s disease (PD) experience anxiety and depression, associated with impaired physical function, high care dependency and mortality. Recently, the United States National Institutes of H…
View article: In vivo overexpression of synaptogyrin‐3 promotes striatal synaptic dopamine uptake in LRRK2 <sup>R1441G</sup> mutant mouse model of Parkinson's disease
In vivo overexpression of synaptogyrin‐3 promotes striatal synaptic dopamine uptake in LRRK2 <sup>R1441G</sup> mutant mouse model of Parkinson's disease Open
Background Leucine‐rich repeat kinase 2 (LRRK2) mutation is a common genetic risk factor of Parkinson's disease (PD). Presynaptic dysfunction is an early pathogenic event associated with dopamine (DA) dysregulation in striatum of the brain…
View article: Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects
Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects Open
View article: Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (SYNGR3) Gene: The Effects of NURR1 on Its Expression
Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (SYNGR3) Gene: The Effects of NURR1 on Its Expression Open
Synaptogyrin-3 (SYNGR3) is a synaptic vesicular membrane protein. Amongst four homologues (SYNGR1 to 4), SYNGR1 and 3 are especially abundant in the brain. SYNGR3 interacts with the dopamine transporter (DAT) to facilitate dopamine (DA) up…
View article: LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease
LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease Open
Mutations in the leucine-rich repeat kinase 2 gene ( LRRK2 ) are one of the most frequent genetic causes of both familial and sporadic Parkinson’s disease (PD). Mounting evidence has demonstrated pathological similarities between LRRK2 -as…
View article: LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease
LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease Open
Mutations in leucine-rich repeat kinase 2 ( LRRK2 ) and glucocerebrosidase ( GBA ) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which a…
View article: Relayed nuclear Overhauser effect weighted (rNOEw) imaging identifies multiple sclerosis
Relayed nuclear Overhauser effect weighted (rNOEw) imaging identifies multiple sclerosis Open
View article: Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2<sup>R1441G</sup> mice
Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2<sup>R1441G</sup> mice Open
Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradatio…
View article: Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2<sup>R1441G</sup> mice
Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2<sup>R1441G</sup> mice Open
Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradatio…
View article: Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2<sup>R1441G</sup>mice
Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2<sup>R1441G</sup>mice Open
Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradatio…
View article: Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2<sup>R1441G</sup> mice
Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2<sup>R1441G</sup> mice Open
Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradatio…
View article: The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease
The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease Open
View article: Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA)
Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA) Open
Parkinson disease (PD) is an age-related neurodegenerative disorder associated with misfolded SNCA/α-synuclein accumulation in brain. Impaired catabolism of SNCA potentiates formation of its toxic oligomers. LRRK2 (leucine-rich repe…
View article: Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA)
Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA) Open
Parkinson disease (PD) is an age-related neurodegenerative disorder associated with misfolded SNCA/α-synuclein accumulation in brain. Impaired catabolism of SNCA potentiates formation of its toxic oligomers. LRRK2 (leucine-rich repe…
View article: Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA)
Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA) Open
Parkinson disease (PD) is an age-related neurodegenerative disorder associated with misfolded SNCA/α-synuclein accumulation in brain. Impaired catabolism of SNCA potentiates formation of its toxic oligomers. LRRK2 (leucine-rich repe…
View article: Activation of hypothalamic <scp>RIP</scp> ‐Cre neurons promotes beiging of <scp>WAT</scp> via sympathetic nervous system
Activation of hypothalamic <span>RIP</span> ‐Cre neurons promotes beiging of <span>WAT</span> via sympathetic nervous system Open
View article: Orbital Ectopic Lymphoid Follicles with Germinal Centers in Aquaporin-4-IgG-Positive Neuromyelitis Optica Spectrum Disorders
Orbital Ectopic Lymphoid Follicles with Germinal Centers in Aquaporin-4-IgG-Positive Neuromyelitis Optica Spectrum Disorders Open
Neuromyelitis optica spectrum disorders (NMOSDs) are important autoimmune central nervous system (CNS) astrocytopathy causing acute myelitis, optic neuritis (ON), and encephalitis associated with significant morbidities and mortality. It i…
View article: Development of phospho-specific Rab protein antibodies to monitor <i>in vivo</i> activity of the LRRK2 Parkinson's disease kinase
Development of phospho-specific Rab protein antibodies to monitor <i>in vivo</i> activity of the LRRK2 Parkinson's disease kinase Open
Mutations that activate the LRRK2 (leucine-rich repeat protein kinase 2) protein kinase predispose to Parkinson's disease, suggesting that LRRK2 inhibitors might have therapeutic benefit. Recent work has revealed that LRRK2 phosphorylates …
View article: Total small vessel disease score and risk of recurrent stroke
Total small vessel disease score and risk of recurrent stroke Open
The total SVD score has predictive value for recurrent stroke after TIA/ischemic stroke. Prediction of recurrence in patients with nonlacunar events highlights the potential role of SVD in wider stroke etiology.
View article: Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson’s disease
Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson’s disease Open
View article: Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice
Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice Open
Our results indicated that chronic APN deficiency inactivated AMPK causing insulin desensitization and elicited AD-like pathogenesis in aged mice which also developed significant cognitive impairments and psychiatric symptoms.
View article: Deficiency of Cks1 Leads to Learning and Long-Term Memory Defects and p27 Dependent Formation of Neuronal Cofilin Aggregates
Deficiency of Cks1 Leads to Learning and Long-Term Memory Defects and p27 Dependent Formation of Neuronal Cofilin Aggregates Open
In mitotic cells, the cyclin-dependent kinase (CDK) subunit protein CKS1 regulates S phase entry by mediating degradation of the CDK inhibitor p27. Although mature neurons lack mitotic CDKs, we found that CKS1 was actively expressed in pos…
View article: Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors
Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors Open
Autosomal dominant mutations that activate the leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson's disease. Recent work has revealed that LRRK2 directly phosphorylates a conserved threonine/serine residue in the effector-bindi…