Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson’s disease

Abstract

Individuals with Parkinson’s disease (PD) often suffer from comorbid depression. P11 (S100A10), a member of the S100 family of proteins, is expressed widely throughout the body and is involved in major depressive disorder and antidepressant response. Central p11 levels are reduced in postmortem tissue from depressed individuals; however, p11 has not yet been investigated in PD patients with depression or those without depression. We investigated p11 levels in postmortem PD brains and assessed whether peripheral p11 levels correlate with disease severity. Substantia nigra, putamen, and cortical p11 protein levels were assessed in postmortem brain samples from PD patients and matched controls. In a different set of postmortem brains, p11 mRNA expression was measured in dopaminergic cells from the substantia nigra. Both p11 protein and mRNA levels were decreased in PD patients. Peripheral p11 protein levels were investigated in distinct leukocyte populations from PD patients with depression and those without depression. Monocyte, natural killer (NK) cell, and cytotoxic T-cell p11 levels were positively associated with the severity of PD, and NK cell p11 levels were positively associated with depression scores. Given that inflammation plays a role in both PD and depression, it is intriguing that peripheral p11 levels are altered in immune cells in both conditions. Our data provide insight into the pathological alterations occurring centrally and peripherally in PD. Moreover, if replicated in other cohorts, p11 could be an easily accessible biomarker for monitoring the severity of PD, especially in the context of comorbid depression.

Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons

“…Whether neurons contribute to these disease features has been an open question. Indeed, some studies revealed progressive activity of SA-b-gal in cultured cerebellar granular neurons and hippocampal neurons (Bhanu et al, 2010;Bigagli et al, 2016;Green et al, 2017). However, there has been debate whether SA-b-gal activity by itself is a sufficient marker for cellular senescence (Severino et al, 2000).…”

Biological and Clinical Implications of Comorbidities in Parkinson’s Disease

“…An easily accessible biomarker that could inform about comorbid depression in PD would be useful to provide individualized treatment of patients. In this regard, a recent study identified that protein levels of S100A10 were associated with depression scores in PD patients with depression compared to those without Green et al ( 2017 ). Similarly, serum levels of BDNF were lower in PD patients with depression than those without depression (Wang et al, 2017 ).…”

“…In the context of diagnosis, some biomarkers may be better suited for identifying PD patients with comorbid diabetes or depression. In this regard, biomarkers identified in shared pathways between PD and diabetes (Santiago and Potashkin, 2013a , 2015b ; Santiago et al, 2014 ), inflammation (Ciaramella et al, 2013 ; Eidson et al, 2017 ) or PD and depression (Santiago et al, 2016 ; Green et al, 2017 ; Wang et al, 2017 ) could be useful diagnostic tools. More recently, an unbiased chemical screen identified the β2-adrenoreceptor (β2AR) as a regulator of SNCA (Mittal et al, 2017 ).…”

Essential roles of S100A10 in Toll-like receptor signaling and immunity to infection

“… 8 – 11 In particular, it is intriguing that expression levels of S100A10 in peripheral blood leukocytes, including monocytes, natural killer cells, and CD8 + T cells, are altered in both depression and Parkinson’s disease. 10 Although the functions of S100A10 have been extensively investigated in the central nervous system, its function in the immune system remains largely unknown.…”