Neuropathological role of alpha-synuclein: major contribution of inflammation in the evolution of both motor and non-motor symptoms of Parkinson’s disease
type: CreativeWork
description: Neuroinflammation is nowadays considered a cardinal pathological feature of Parkinson’s disease (PD), in which glial cells lose their homeostatic function in favour of a pro-inflammatory profile. Such sustained glial response within the brain parenchyma is characterized by a chronic release of a number of pro-inflammatory mediators, likely driven by pathological interactions with toxic forms of α-Synuclein (αSyn). Moreover, the contribution of the peripheral immune system to PD neuropathology has been demonstrated, promoting the view of PD as a systemic pathology. While the contribution of inflammation to the neuropathology of motor symptoms has been ascertained, its role in non-motor symptoms is still under-investigated, particularly in relation to cognitive disturbances. Here, we targeted inflammation in PD by testing the immunomodulatory imide drug (IMiD) Pomalidomide (Pom) for its disease-modifying properties against motor deficits in a translational rat model of PD based on the intranigral infusion of toxic oligomers of human α-synuclein (H-αSynOs) (study I). Moreover, we investigated the contribution of neuroinflammation in PD cognitive symptoms, in the same PD preclinical model (study II). Study I: The neuroprotective effect of Pom (20 mg/kg; i.p. three times/week for two months) was tested in the early stage of the disease. We found that the infusion of H-αSynOs induced an impairment in motor performance that was fully rescued by Pom, as assessed via a battery of motor tests. Moreover, H-αSynOs-infused rats displayed a 40–45% cell loss within the substantia nigra (SN), that was largely abolished by Pom. The inflammatory response to H-αSynOs infusion and the Pom treatment was evaluated both in CNS and peripherally. After H-αSynOs infusion, microglia displayed a proinflammatory profile, producing a large amount of the cytokine Tumour Necrosis Factor (TNF)-α. In contrast, Pom inhibited the TNF-α overproduction and elevated the anti-inflammatory cytokine Interle…
abstract: Neuroinflammation is nowadays considered a cardinal pathological feature of Parkinson’s disease (PD), in which glial cells lose their homeostatic function in favour of a pro-inflammatory profile. Such sustained glial response within the brain parenchyma is characterized by a chronic release of a number of pro-inflammatory mediators, likely driven by pathological interactions with toxic forms of α-Synuclein (αSyn). Moreover, the contribution of the peripheral immune system to PD neuropathology has been demonstrated, promoting the view of PD as a systemic pathology. While the contribution of inflammation to the neuropathology of motor symptoms has been ascertained, its role in non-motor symptoms is still under-investigated, particularly in relation to cognitive disturbances. Here, we targeted inflammation in PD by testing the immunomodulatory imide drug (IMiD) Pomalidomide (Pom) for its disease-modifying properties against motor deficits in a translational rat model of PD based on the intranigral infusion of toxic oligomers of human α-synuclein (H-αSynOs) (study I). Moreover, we investigated the contribution of neuroinflammation in PD cognitive symptoms, in the same PD preclinical model (study II). Study I: The neuroprotective effect of Pom (20 mg/kg; i.p. three times/week for two months) was tested in the early stage of the disease. We found that the infusion of H-αSynOs induced an impairment in motor performance that was fully rescued by Pom, as assessed via a battery of motor tests. Moreover, H-αSynOs-infused rats displayed a 40–45% cell loss within the substantia nigra (SN), that was largely abolished by Pom. The inflammatory response to H-αSynOs infusion and the Pom treatment was evaluated both in CNS and peripherally. After H-αSynOs infusion, microglia displayed a proinflammatory profile, producing a large amount of the cytokine Tumour Necrosis Factor (TNF)-α. In contrast, Pom inhibited the TNF-α overproduction and elevated the anti-inflammatory cytokine Interle…
author: PALMAS, MARIA FRANCESCA
language: eng
keywords: Settore BIO/14 - Farmacologia
date published: 2023-01-16T00:00:00+01:00
date modified: 2026-07-24T01:29:52Z
provider: Università di Cagliari
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Cagliari

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property ID: Handle
value: https://hdl.handle.net/11584/356461