Parkinson’s disease (PD) is a complex, multisystem disorder characterised by alpha synuclein pathology, degeneration of nigrostriatal dopaminergic neurons, multifactorial pathogenetic mechanisms and expression of a plethora of motor and non-motor symptoms. Animal models of PD have already been instructive in helping us unravel some of these aspects. However, much remains to be discovered, requiring continued interrogation by the research community. In contrast to the situation for many neurological disorders, PD benefits from of a wide range of available animal models (pharmacological, toxin, genetic and alpha-synuclein) but this makes selection of the optimal one for a given study difficult. This is especially so when a study demands a model that displays a specific combination of features. While many excellent reviews of animal models already exist, this review takes a different approach with the intention of more readily informing this decision-making process. We have considered each feature of PD in turn - aetiology, pathology, pathogenesis, motor dysfunctions and non-motor symptoms - highlighting those animal models that replicate each. By compiling easily accessible tables and figures, we aim to provide the reader with a simple, go-to resource for selecting the optimal animal model of PD to suit their research needs.

Background NLRP3‐driven inflammatory responses by circulating and lung‐resident monocytes are critical drivers of asthma pathogenesis. Autophagy restrains NLRP3‐induced monocyte activation in asthma models. Yet, the effects of autophagy and its master regulator, transcription factor EB (TFEB), on monocyte responses in human asthma remain unexplored. Here, we investigated whether activation of autophagy and TFEB signaling suppress inflammatory monocyte responses in asthmatic individuals. Methods Peripheral blood CD14+ monocytes from asthmatic patients (n = 83) and healthy controls (n = 46) were stimulated with LPS/ATP to induce NLRP3 activation with or without the autophagy inducer, rapamycin. ASC specks, caspase‐1 activation, IL‐1β and IL‐18 levels, mitochondrial function, ROS release, and mTORC1 signaling were examined. Autophagy was evaluated by LC3 puncta formation, p62/SQSTM1 degradation and TFEB activation. In a severe asthma (SA) model, we investigated the role of NLRP3 signaling using Nlrp3−/− mice and/or MCC950 administration, and the effects of TFEB activation using myeloid‐specific TFEB‐overexpressing mice or administration of the TFEB activator, trehalose. Results We observed increased NLRP3 inflammasome activation, concomitant with impaired autophagy in circulating monocytes that correlated with asthma severity. SA patients also exhibited mitochondrial dysfunction and ROS accumulation. Autophagy failed to inhibit NLRP3‐driven monocyte responses, due to defective TFEB activation and excessive mTORC1 signaling. NLRP3 blockade restrained inflammatory cytokine release and linked airway disease. TFEB activation restored impaired autophagy, attenuated NLRP3‐driven pulmonary inflammation, and ameliorated SA phenotype. Conclusions Our studies uncover a crucial role for TFEB‐mediated reprogramming of monocyte inflammatory responses, raising the prospect that this pathway can be therapeutically harnessed for the management of SA.

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM parasomnia that often predicts the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of α-synucleinopathy, we now demonstrate striking REM and NREM electroencephalographic sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry.

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a rare parasomnia that may predict the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of α-synucleinopathy, we now demonstrate striking REM and NREM sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry.

Background Pain is a common non-motor symptom of Parkinson`s disease (PD), however, its pathomechanism remains elusive. Objective We aimed to investigate the local gene expression of selected proinflammatory mediators in patients with PD and correlated our data with patients`pain phenotype. Methods We recruited 30 patients with PD and 30 healthy controls. Pain intensity of patients was assessed using the Numeric Rating Scale (NRS) and patients were stratified into PD pain (NRS≥4) and PD No Pain (NRS<4) subgroups. Skin punch biopsies were immunoassayed for protein-gene product 9.5 as a pan-neuronal marker and intraepidermal nerve fiber density (IEFND). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to assess the gene expression of inflammatory mediators in the skin compared to controls. Results Patients with PD had lower distal IENFD compared to healthy controls. In skin samples, IL-2 (p<0.001) and TNF-α (p<0.01) were expressed higher in PD patients compared to controls. IL-1β (p<0.05) was expressed higher in the PD pain group compared to healthy controls. PD patients with pain receiving analgesics had a lower expression of TNF-α (p<0.05) in the skin compared to those not receiving treatment. Conclusions Our data suggest the occurrence of a local, peripheral inflammatory response in the skin in PD, but do not support this being a relevant factor contributing to pain in PD.