Exploring the Involvement of PINK1 in Parkinson’s Disease: A Scanning Tunnelling Microscopy Study of Electron Transfer in Synthetic DNA Samples

Main Article Content

Muhammad Hanif Che Lah
Mohammed Faruque Reza
Shaharum Shamsuddin
Isao Watanabe
Jafri Malin Abdullah

Abstract

Background: Parkinson’s disease (PD) is a neurodegenerative disorder with a complex aetiology involving several genetic and environmental factors. Although no clear evidence of a direct link between the electronic features of DNA and PD has been found, elucidating the role of DNA in cellular function and dysfunction could provide valuable insights into the mechanisms of the disease (e.g. mutations occurring in the phosphatase and tensin homolog [PTEN]-induced kinase 1 [PINK1] DNA of PD). This study aimed to analyse topographic images and measure the electronic conductivity of synthetic normal and mutant PINK1 DNA molecules.


Methods: Two 15-mer synthetic oligonucleotides of Oligo1 normal PINK1 (5’-CAG CTG CTG GAA GGC-3’) and Oligo2 mutant PINK1 (5’-CAG CTG CCG GAA GGC-3’) were measured using scanning tunnelling microscopy and spectroscopy.


Results: The study’s findings revealed that the mean values of the voltage gap (Vg) between Oligo1 normal and Oligo2 mutant PINK1 DNA molecules at the mutation region A2–C2 are 1.204 ± 0.198 V and 0.676 ± 0.495 V, respectively, indicating differences in the electronic properties between the Oligo1 normal and Oligo2 mutant PINK1 DNA molecules. However, the mean Vg values of Oligo1 normal and Oligo2 mutant PINK1 DNA molecules were found to not significantly differ from each other (P = 0.162 > ? = 0.05).


Conclusion: The study found that the voltage gap between normal and mutant PINK1 DNA molecules is not significantly different, suggesting that DNA sequence differences may not directly alter electrical properties. However, PINK1 mutations play a role in early-onset PD due to mitochondrial dysfunction, and future therapies should focus on restoring PINK1-Parkin signalling and mitochondrial health.

Article Details

How to Cite
1.
Che Lah MH, Reza MF, Shamsuddin S, Watanabe I, Abdullah JM. Exploring the Involvement of PINK1 in Parkinson’s Disease: A Scanning Tunnelling Microscopy Study of Electron Transfer in Synthetic DNA Samples. Malays J Med Sci [Internet]. 2025 Aug. 30 [cited 2025 Nov. 20];32(4):129–144. Available from: https://ejournal.usm.my/mjms/article/view/mjms_vol32-no4-2025_8
Section
Original Articles

References

Chopade P, Chopade N, Zhao Z, Mitragotri S, Liao R, Chandran Suja V. Alzheimer’s and Parkinson’s disease therapies in the clinic. Bioeng Transl Med. 2023;8(1):e10367. https://doi.org/10.1002/btm2.10367

Monzio Compagnoni G, Di Fonzo A, Corti S, Comi GP, Bresolin N, Masliah E. The role of mitochondria in neurodegenerative diseases: The lesson from Alzheimer’s disease and Parkinson’s disease. Mol Neurobiol. 2020;57:2959–2980. https://doi.org/10.1007/s12035-020-01926-1

Reddy AP, Ravichandran J, Carkaci-Salli N. Neural regeneration therapies for Alzheimer’s and Parkinson’s disease-related disorders. Biochim Biophys Acta Mol Basis Dis. 2020;1866(4):165506. https://doi.org/10.1016/j.bbadis.2019.06.020

Luo M, Gan R-Y, Li B-Y, Mao Q-Q, Shang A, Xu X-Y, et al. Effects and mechanisms of tea on Parkinson’s disease, Alzheimer’s disease and depression. Food Rev Int. 2023;39(1):278–306. https://doi.org/10.1080/87559129.2021.1904413

Gonzalez-Hunt CP, Sanders LH. DNA damage and repair in Parkinson’s disease: Recent advances and new opportunities. J Neurosci Res. 2021;99(1):180–189. https://doi.org/10.1002/jnr.24592

Thomas B, Beal MF. Parkinson’s disease. Hum Mol Genet. 2007;16(R2):R183–R194. https://doi.org/10.1093/hmg/ddm159

Ou Z, Pan J, Tang S, Duan D, Yu D, Nong H, et al. Global trends in the incidence, prevalence, and years lived with disability of Parkinson’s disease in 204 countries/territories from 1990 to 2019. Front Public Health. 2021;9:776847. https://doi.org/10.3389/fpubh.2021.776847

Singh G, Sharma M, Kumar GA, Rao NG, Prasad K, Mathur P, et al. The burden of neurological disorders across the states of India: the Global Burden of Disease Study 1990–2019. Lancet Glob Health. 2021;9(8):e1129–e1144. https://doi.org/10.1016/S2214-109X(21)00164-9

Deuschl G, Beghi E, Fazekas F, Varga T, Christoforidi KA, Sipido E, et al. The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017. Lancet Public Health. 2020;5(10):e551–e567. https://doi.org/10.1016/S2468-2667(20)30190-0

Lampropoulos IC, Malli F, Sinani O, Gourgoulianis KI, Xiromerisiou G. Worldwide trends in mortality related to Parkinson’s disease in the period of 1994–2019: analysis of vital registration data from the WHO mortality database. Front Neurol. 2022;13:956440. https://doi.org/10.3389/fneur.2022.956440

Abdul Murad NA, Sulaiman SA, Ahmad-Annuar A, Mohamed Ibrahim N, Mohamed W, Md Rani SA, et al. Genetic and molecular diversity in Parkinson’s disease. Front Aging Neurosci. 2022;14:1094914. https://doi.org/10.3389/fnagi.2022.1094914

Kim J-M, Lee J-Y, Kim HJ, Kim JS, Shin E-S, Cho J-H, et al. The LRRK2 G2385R variant is a risk factor for sporadic Parkinson’s disease in the Korean population. Parkinsonism Relat Disord. 2010;16(2):85–88. https://doi.org/10.1016/j.parkreldis.2009.10.004

Zhao Y, Qin L, Pan H, Liu Z, Jiang L, He Y, et al. The role of genetics in Parkinson’s disease: a large cohort study in Chinese mainland population. Brain. 2020;143(7):2220–2234. https://doi.org/10.1093/brain/awaa167

Gopalai AA, Lim S-Y, Chua JY, Tey S, Lim TT, Mohamed Ibrahim N, et al. LRRK2 G2385R and R1628P mutations are associated with an increased risk of Parkinson’s disease in the Malaysian population. Biomed Res Int. 2014;2014(1):867321. https://doi.org/10.1155/2014/867321

Tan AH, Lohmann K, Tay YW, Lim JL, Ahmad-Annuar A, Ramli N, et al. PINK1 p.Leu347Pro mutations in Malays: Prevalence and illustrative cases. Parkinsonism Relat Disord. 2020;79:34–39. https://doi.org/10.1016/j.parkreldis.2020.08.015

Lim JL, Lohmann K, Tan AH, Tay YW, Ibrahim KA, Abdul Aziz Z, et al. Glucocerebrosidase (GBA) gene variants in a multi-ethnic Asian cohort with Parkinson’s disease: mutational spectrum and clinical features. J Neural Transm. 2022;129(1):37–48. https://doi.org/10.1007/s00702-021-02421-0

Tay YW, Tan AH, Lim JL, Lohmann K, Ibrahim KA, Abdul Aziz ZA, et al. Genetic study of early-onset Parkinson’s disease in the Malaysian population. Parkinsonism Relat Disord. 2023;111:105399. https://doi.org/10.1016/j.parkreldis.2023.105399

Rodríguez-Galván A, Contreras-Torres FF. Scanning tunneling microscopy of biological structures: an elusive goal for many years. Nanomaterials. 2022;12(17):3013. https://doi.org/10.3390/nano12173013

Ghoderao P, Sahare S, Lee S-L, Sonar P. Envision and appraisal of biomolecules and their interactions through scanning probe microscopy. Small Struct. 2023;4(7):2200273. https://doi.org/10.1002/sstr.202200273

Jin J, Li S, Wang Z, Lu Y, Liu X, Wang L. Polymorphic pairing configurations of guanine and cytosine at the water-HOPG interface. Langmuir. 2021;37(12):3761–3765. https://doi.org/10.1021/acs.langmuir.1c00296

Arscott P, Bloomfield V. Scanning tunnelling microscopy of nucleic acids and polynucleotides. Ultramicroscopy. 1990;33(2):127–131. https://doi.org/10.1016/0304-3991(90)90015-E

Integrated DNA Technologies (IDT). 1stBASE bulletin – what is standard desalted oligos. [Internet]. Seri Kembangan, Selangor: First Base Laboratories Sdn Bhd; 2017. [Retrieved 2025 Jan 29]. Available at: https://base-asia.com/downloads/promotions/FirstBASE-Bulletin-What-is-Standard-Desalted-Oligos-A4.pdf

Zareie MH, Lukins PB. Atomic-resolution STM structure of DNA and localization of the retinoic acid binding site. Biochem Biophys Res Commun. 2003;303(1):153–159. https://doi.org/10.1016/S0006-291X(03)00298-5

Akhmetova AI, Yaminsky IV. High resolution imaging of viruses: scanning probe microscopy and related techniques. Methods. 2022;197:30–38. https://doi.org/10.1016/j.ymeth.2021.06.011

Allison DP, Thompson JR, Jacobson KB, Warmack RJ, Ferrell TL. Scanning tunneling microscopy and spectroscopy of plasmid

DNA. Scanning Microsc. 1990;4(3):2. https://digitalcommons.usu.edu/microscopy/vol4/iss3/2/

Yarotski DA, Kilina SV, Talin AA, Tretiak S, Prezhdo OV, Balatsky AV, et al. Scanning tunneling microscopy of DNA-wrapped carbon nanotubes. Nano Lett. 2009;9(1):12–17. https://doi.org/10.1021/nl801455t

Keller D, Bustamante C, Keller RW. Imaging of single uncoated DNA molecules by scanning tunneling microscopy. Proc Natl Acad Sci. 1989;86(14):5356–5360. https://doi.org/10.1073/pnas.86.14.5356

Iijima M, Watabe T, Ishii S, Koshio A, Yamaguchi T, Bandow S, et al. Fabrication and STM-characterization of novel hybrid materials of DNA/carbon nanotube. Chem Phys Lett. 2005;414(4–6):520–524. https://doi.org/10.1016/j.cplett.2005.09.032

Tanaka H, Hamai C, Kanno T, Kawai T. High-resolution scanning tunneling microscopy imaging of DNA molecules on Cu (111) surfaces. Surf Sci. 1999;432(3):L611–L616. https://doi.org/10.1016/S0039-6028(99)00623-8

Clemmer CR, Beebe TP Jr. A review of graphite and gold surface studies for use as substrates in biological scanning tunneling microscopy studies. Scanning Microsc. 1992;6(2):2.

https://digitalcommons.usu.edu/microscopy/vol6/iss2/2/

Mazurkiewicz J, Mearns FJ, Losic D, Weeks L, Waclawik ER, Rogers CT, et al. Cryogenic cleavage used in gold substrate production. J Vac Sci Technol B. 2002;20(6):2265–2270. https://doi.org/10.1116/1.1518968

Leggett G, Davies M, Jackson D, Tendler S. Scanning probe microscopy of biomolecules and polymeric biomaterials. J Electron Spectrosc Relat Phenom. 1996;81(3):249–268. https://doi.org/10.1016/0368-2048(95)02527-8

Moult I, Herve M, Pennec Y. Ultrafast spectroscopy with a scanning tunneling microscope. Appl Phys

Lett. 2011;98(23):233103. https://doi.org/10.1063/1.3597351

Chang H, Bard AJ. Observation and characterization by scanning tunneling microscopy of structures generated by cleaving highly oriented pyrolytic graphite. Langmuir. 1991;7(6):1143–1153. https://doi.org/10.1021/la00054a021

Lapshin RV. STM observation of a box-shaped graphene nanostructure appeared after mechanical cleavage of pyrolytic graphite. Appl Surf Sci. 2016;360:451–460. https://doi.org/10.1016/j.apsusc.2015.09.222

Bellamy-Carter A, Roche C, Anderson HL, Saywell A. Self-assembly of a strapped linear porphyrin oligomer on HOPG. Sci Rep. 2021;11(1):20388. https://doi.org/10.1038/s41598-021-99881-x

Beebe TP Jr, Wilson TE, Ogletree DF, Katz JE, Balhorn R, Salmeron MB, et al. Direct observation of native DNA structures

with the scanning tunneling microscope. Science. 1989;243(4889):370–372. https://doi.org/10.1126/science.2911747

Lee G, Arscott PG, Bloomfield VA, Evans DF. Scanning tunneling microscopy of nucleic acids. Science. 1989;244(4903):475–477. https://doi.org/10.1126/science.2470146

Alliata D, Andolfi L, Cannistraro S. Tip to substrate distances in STM imaging of biomolecules. Ultramicroscopy. 2004;101(2–4):231–240. https://doi.org/10.1016/j.ultramic.2004.06.005

Sørensen AH, Hvid U, Mortensen MW, Mørch KA. Preparation of platinum/iridium scanning probe microscopy tips. Rev Sci Instrum. 1999;70(7):3059–3067. https://doi.org/10.1063/1.1149891

Collins AM. Chapter 5 – Physical techniques. In: Collins AM, editor. Nanotechnology cookbook: practical, reliable and jargon-free experimental procedures. Netherlands: Elsevier Science; 2012. pp. 205–253. https://doi.org/10.1016/B978-0-08-097172-8.00005-9

Tewari S, Bastiaans KM, Allan MP, van Ruitenbeek JM. Robust procedure for creating and characterizing the atomic structure of scanning tunneling microscope tips. Beilstein J Nanotechnol. 2017;8(1):2389–2395. https://doi.org/10.3762/bjnano.8.238

Wiesendanger R. Scanning probe microscopy and spectroscopy: methods and applications. United Kingdom: Cambridge University Press; 1994. pp. 147–148. https://doi.org/10.1017/CBO9780511524356

Shapir E, Sagiv L, Molotsky T, Kotlyar AB, Di Felice R, Porath D. Electronic structure of G4-DNA by scanning tunneling spectroscopy. J Phys Chem C. 2010;114(50):22079–22084. https://doi.org/10.1021/jp107952y

Chen CJ. Introduction to scanning tunneling microscopy. 3rd ed. United Kingdom: Oxford University Press; 2021. pp. 363–366. https://doi.org/10.1093/oso/9780198856559.003.0015

Zhuravel R, Stern A, Fardian-Melamed N, Eidelshtein G, Katrivas L, Rotem D, et al. Advances in synthesis and measurement of charge transport in DNA-based derivatives. Adv Mater. 2018;30(41):1706984. https://doi.org/10.1002/adma.201706984

Fardian-Melamed N, Eidelshtein G, Rotem D, Kotlyar A, Porath D. Scanning tunneling microscopy and spectroscopy of novel silver-containing DNA molecules. Adv Mater. 2019;31(35):1902816. https://doi.org/10.1002/adma.201902816

Shapir E, Cohen H, Calzolari A, Cavazzoni C, Ryndyk DA, Cuniberti G, et al. Electronic structure of single DNA molecules resolved by transverse scanning tunnelling spectroscopy. Nat Mater. 2008;7(1):68–74. https://doi.org/10.1038/nmat2060

Horcas I, Fernández R, Gomez-Rodriguez J, Colchero J, Gómez-Herrero J, Baro A. WSXM: a software for scanning probe microscopy and a tool for nanotechnology. Rev Sci Instrum. 2007;78(1):013705. https://doi.org/10.1063/1.2432410

Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 2012;4:17. https://doi.org/10.1186/1758-2946-4-17

Mishra P, Pandey CM, Singh U, Gupta A, Sahu C, Keshri A. Descriptive statistics and normality tests for statistical data. Ann Card Anaesth. 2019;22(1):67–72. https://doi.org/10.4103/aca.ACA_157_18

Nahm FS. Nonparametric statistical tests for the continuous data: the basic concept and the practical use. Korean J Anesthesiol. 2016;69(1):8–14. https://doi.org/10.4097/kjae.2016.69.1.8

Vrbin CM. Parametric or nonparametric statistical tests: considerations when choosing the most appropriate option for your data. Cytopathology. 2022;33(6):663–667. https://doi.org/10.1111/cyt.13174

Heiman GW. Basic statistics for the behavioral sciences. 7th ed. Belmont (CA): Cengage Learning; 2013. p. 270

Ahad NA, Yin TS, Othman AR, Yaacob CR. Sensitivity of normality tests to non-normal data. Sains Malaysiana. 2011;40(6):637–641.

Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika. 1965;52(3–4):591–611. https://doi.org/10.1093/biomet/52.3-4.591

Siegel AF. Chapter 15 – ANOVA: testing for differences among many samples and much more. In: Siegel AF, editor. Practical business statistics. 7th ed. London: Academic Press; 2016. p. 475

Zhou Y, Zhu Y, Wong WK. Statistical tests for homogeneity of variance for clinical trials and recommendations. Contemp Clin Trials Commun. 2023;33:101119. https://doi.org/10.1016/j.conctc.2023.101119

Barinov NA, Ivanov DA, Dubrovin EV, Klinov DV. Atomic force microscopy investigation of DNA denaturation on a highly oriented pyrolytic graphite surface. Int J Biol Macromol. 2024;267:131630. https://doi.org/10.1016/j.ijbiomac.2024.131630

Thill A, Spalla O. Aggregation due to capillary forces during drying of particle submonolayers. Colloids Surf A Physicochem Eng Asp. 2003;217(1–3):143–151. https://doi.org/10.1016/S0927-7757(02)00569-1

Liu Z, Zhao L, Zu Y, Tan S, Wang Y, Zhang Y. Unusual DNA structures formed on bare highly oriented pyrolytic graphite surfaces studied by atomic force microscopy. Microsc Microanal. 2013;19(3):544–552. https://doi.org/10.1017/S1431927613000275

Hellenthal C, Heimbuch R, Sotthewes K, Kooij ES, Zandvliet HJW. Determining the local density of states in the constant current STM mode. Phys Rev B. 2013;88(3):035425. https://doi.org/10.1103/PhysRevB.88.035425

Srivastava R. The role of proton transfer on mutations. Front Chem. 2019;7:536. https://doi.org/10.3389/fchem.2019.00536

Xu M, Endres RG, Arakawa Y. The electronic properties of DNA bases. Small. 2007;3(9):1539–1543. https://doi.org/10.1002/smll.200600732

Hamers RJ, Tromp RM, Demuth JE. Surface electronic structure of Si (111)-(7×7) resolved in real space. Phys Rev Lett. 1986;56(18):1972. https://doi.org/10.1103/PhysRevLett.56.1972