I lead a research team in HKU focusing mainly on Parkinson's disease (PD), its etiology, pathogenesis and exploring therapeutic methods to modify these processes. Our earlier research described how a ubiquitous xenobiotic enzyme, catechol-O-methyltransferase (COMT) provided the link between the effects of estrogen and PD. This project delivered tangible materials including human COMT antibodies and a patented COMT ELISA assay containing a unique synthetic 18 amino acid polypeptide protein tag. This enzyme assay can quantify the estrogenic effects of environmental pollutants, such as PCBs and plasticizers linked to cancer and neurodegeneration. We have previously explored mitochondrial dysfunction, an important pathogenic process involved in PD. We described and elucidated some of the neuroprotective mechanisms of mitochondrial neuronal uncoupling proteins (UCPs) in experimental models of PD. We have developed methods and materials including antibodies to human neuronal uncoupling proteins (UCP4 and 5). Our studies uncovered a novel link between UCPs and nuclear-factor kappa-B (NF-kB), and more specifically the c-Rel pro-survival pathway, which can be a potential therapeutic target in PD. In parallel studies, we described the beneficial effects of leptin (a regulator of metabolism) on neuronal survival being mediated via UCP2, supporting a link between metabolic pathways and pathogenic processes in PD. We also elucidated how UCP4 interacted with mitochondrial Complex II to preserve ATP synthesis under cellular stress.
More recently, we have developed a unique colony of an experimental mouse model with a leucine-rich repeat kinase-2 (LRRK2) knockin mutation (C57BL/6N background) based on the mutation found in familial PD. Our current work focuses on pathogenic mechanisms and developing therapeutic methods to modify the course of LRRK2-related and sporadic idiopathic PD. One key aim is to deliver unique materials in unraveling the pathogenic processes of PD, in particular developing novel methods to assay the rates of different forms of autophagy.
- Ho PW, Chang EE, Leung CT , Liu HF, Malki Y, Pang SY, Choi ZY, Liang Y, Lai WS, Ruan Y, Leung KM, Yung S, Mak JC, Kung MH, Ramsden DB, Ho SL. Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects. NPJ Parkinson's Disease. 2022 Sep 10;8(1):115. doi: 10.1038/s41531-022-00386-9.
- Li LF, Ho PW, Liu HF, Pang SY, Chang ES, Choi ZY, Malki Y, Kung MH, Ramsden DB, Ho SL. Transcriptional regulation of synaptic vesicle protein synaptogyrin-3 (SYNGR3) gene: NURR1 effects on its expression. Int J Mol Sci. 2022 Mar 26;23(7):3646. doi: 10.3390/ijms23073646.
- Chang EE, Ho PW, Liu HF, Pang SY, Leung CT, Malki Y, Choi ZY, Ramsden DB, Ho SL. LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease. Translational Neurodegeneration. 2022 Feb 14;11(1):10. doi: 10.1186/s40035-022-00285-2.
- Pang SY, Lo RNM, Ho PW, Liu HF, Chang EE, Leung CT, Malki Y, Choi ZY, Wong WY, Kung MH, Ramsden DB, Ho SL. LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease. Translational Neurodegeneration. 2022 Jan 31;11(1):5. doi: 10.1186/s40035-022-00281-6.
- Vignando M, FFytche D, Lewis SJG, Lee PH, Chung SJ, Weil RS, Hu MT, Mackay CE, Griffanti L, Pins D, Dujardin K, Jardri R, Taylor JP, Firbank M, McAlonan G, Mak HKF, Ho SL, Mehta MA. Mapping brain structural differences and neuroreceptor correlates in Parkinson’s disease visual hallucinations. Nature Communication. 2022 Jan 26;13(1):519. doi: 10.1038/s41467-022-28087-0.
- Klionsky DJ, Abdel-Aziz AK, Abdelfatah S,…Leung CT,…Liu HF…,Ho, PW, Ho SL,… Ramsden DB…Sluimer JC, Stallings CL, Tong CK. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280. Epub 2021 Feb 8.
- Liu HF, Ho PWL, Leung CT, Pang SY, Chang EE, Choi ZY, Kung MH, Ramsden DB, Ho SL. Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2 R1441G mice. Autophagy. 2020 Dec 10:1-25. doi: 10.1080/15548627.2020.1850008.
- Pang SY, Ho PW, Liu HF, Leung CT, Li LF, Chang EE, Ramsden DB, Ho SL. The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease. Translational Neurodegeneration. 2019 Aug 16;8:23. doi: 10.1186/s40035-019-0165-9. eCollection 2019.
- Ho PW, Leung CT, Liu HF, Pang SY, Lam CSC, Xian JW, Li LF, Kung MH, Ramsden DB, Ho SL. (2019) Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson's disease: role for therapeutic activation of chaperone-mediated autophagy (CMA). Autophagy. 2019 Apr 14:1-24. doi: 10.1080/15548627.2019.1603545.
- Pang SY, Teo KC, Hsu JS, Chang RSK, Li MX, Sham PC, Ho SL. (2017) The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review. Translational Neurodegeneration. 6:27. doi: 10.1186/s40035-017-0098-0.
|Project Title||Funding Scheme||Amount (HKD)|
|Pathophysiological study of Parkinson's disease associated with leucine-rich repeat kinase 2 (LRRK2) gene mutation||Health and Medical Research Fund (HMRF), Food & Health Bureau, HKSAR Government (August 2013)||$928,040|
|Therapeutic effects of Saracatinib to prevent accumulation of alpha synuclein in Parkinson’s disease.||AstraZeneca Open Innovation (June 2017)||$327,750|
|Therapeutic effects of brain-penetrable inhibitors to prevent accumulation of pathogenic alpha-synuclein oligomers in Parkinson's disease.||Health and Medical Research Fund (HMRF), Food & Health Bureau, HKSAR Government (Jan 2018)||$1,175,760|
|Pathophysiological study of synaptic vesicle protein synaptogyrin3 (SYNGR3) in Parkinson's disease.||Health and Medical Research Fund (HMRF), Food & Health Bureau, HKSAR Government (Feb 2018)||$1,195,760|
|Defective autophagic clearance of damaged mitochondria (mitophagy) as potential therapeutic target of Parkinson’s||Health and Medical Research Fund (HMRF). HKSAR Government (March 2019)||$1,469,224|
- Founding Director & Chairperson, Hong Kong Parkinson's Disease Foundation (2002 to date).
- Chairperson, Advisory Committee, Dept of Rehabilitation Sciences, Polytechnic University, Hong Kong (2014 to 2020)
Editorial Board Memberships
- Clinical Neuropharmacology, Editorial Board Member (2006-2008), Associate Editor, (2008 to 2022)
- Brain and Behavior, Editorial Board Member (2011 to 2022)
- Translational Neurodegeneration, Section Editor & Editorial Board Member (2011 to date)
Human catechol-O-methyltransferase (COMT) assay. Listed inventors: PWL Ho, DB Ramsden, SL Ho.
- US patent granted on 6th January 2015; patent no. US 8,927,225 B2
- China patent granted on 12th November 2014; patent no. ZL 200980138401.0
- European patent granted on 23rd October 2013; patent no. 2328909