The Role of Pericytes in PD

Selçuk Polat
Koç University Graduate School of Health Sciences
Neuroscience MSc
 Pericytes and Parkinson’s disease: An overview

• Pericytes possess little or no endogenous α-synuclein

• In Parkinson’s disease, pericytes endocytose alpha-synuclein.
• Pericytes degrade alpha-synuclein by ubiquitin-proteasomal and lysosomal
pathways. In PD brains, pericytes express increased lysosomes to
compensate for excessive alpha-synuclein accumulation.
• Excessive alpha-synuclein causes stress and apoptosis on pericytes
(Stevenson & Dieriks, 2023).
Pericyte response to α-synuclein aggregates in healthy and PD brains

(Stevenson & Dieriks, 2023)

• α-synuclein overexpression
causes pericyte activation
and an initial increase in
vascular density followed
by decrease.
• An initial compensatory
angiogenesis followed by
vascular regression at later
disease stages

(Elobi et al., 2021)

In PD brains, there is increased vascular leakage

(Elobi et al., 2021)

In PD brains, there is an initial increase and a decrease in vascular density, and no change of
pericyte density

(Elobi et al., 2021)

α-synuclein aggregation causes pericyte activation

(Elobi et al., 2021)

Pericytes degrade α-synuclein

(Stevenson et al., 2022)

PD pericytes showed increased number of lysosomal granules to tackle with α-synuclein challenge

(Stevenson et al., 2022)

MG132, a ubiquitin Proteasome inhibitor, and α-synuclein overlap causes causes cell deth and
ROS production

(Stevenson et al., 2022)

MG132, a ubiquitin-proteasome inhibitor, along with α-synuclein, causes cell death

(Stevenson et al., 2022)

 Future Directions

• Investigating the effect of interactions of pericytes with other

cells in the Neurovascular Unit through co-culture studies,
three-dimensional organoid-based tissue-mimicking systems,
and isolated human blood vessels, blood vessel organoids and
in vivo models of chimeric human blood vessels (Stevenson &
Dieriks, 2023; Stevenson et al., 2022).
• Signaling mechanisms governing pericyte interactions with
other cells: PDGF, VEGF, TGF-Beta.
Our Study:
•4 groups:
1.Contol – Vehicle
2.Control – Rotenone
3.PA – Vehicle
4.PA – Rotenone
•Behavioral Tests every week, for one month, five times: Rotarod test, OFT,
Cylinder test
•Measuring TH-positive cells in Substantia Nigra
•Apomorphine challenge
•Vascular Leakage
•Do astrocytes or microglia take up excessive α-synuclein to compensate for
the absence of pericytes?
 References

• Elabi, O., Gaceb, A., Carlsson, R., Padel, T., Soylu-Kucharz, R., Cortijo, I., Li, W., Li, J.-
Y., & Paul, G. (2021). Human α-synuclein overexpression in a mouse model of
parkinson’s disease leads to vascular pathology, blood brain barrier leakage
and Pericyte activation. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-
020-80889-8
• Stevenson, Taylor J., Johnson, R. H., Savistchenko, J., Rustenhoven, J., Woolf, Z.,
Smyth, L. C., Murray, H. C., Faull, R. L., Correia, J., Schweder, P., Heppner, P.,
Turner, C., Melki, R., Dieriks, B. V., Curtis, M. A., & Dragunow, M. (2022).
Pericytes take up and degrade α-synuclein but succumb to apoptosis under cellular
stress. Scientific Reports, 12(1). https://doi.org/10.1038/s41598-022-20261-
0
• Stevenson, Taylor John, & Dieriks, B. V. (2023). Wrapping up the role of pericytes in
parkinson’s disease. Neural Regeneration Research, 18(11), 2395–2396.
https://doi.org/10.4103/1673- 5374.371362