Topic: Lewy bodies

The major neuropathologic feature of Parkinson’s disease is the presence of widespread intracellular inclusions of α-synuclein known as Lewy bodies. Evidence suggests that these misfolded protein inclusions spread through the brain with disease progression. Changes in synaptic function precede neurodegeneration, and this extracellular α-synuclein can affect synaptic transmission. However, whether and how the spreading of α-synuclein aggregates modulates synaptic function before neuronal loss remains unknown. In the present study, we investigated the effect of intrastriatal injection of α-synuc

Parkinson’s disease (PD) is a neurodegenerative disorder that is mainly characterised by the loss of dopaminergic neurons in the substantia nigra as well as the presence of aggregates called Lewy bodies which consist mostly of alpha-synuclein. Astrocytes and microglia are increasingly being regarded as key players in PD-associated neurodegeneration, and these become ‘activated’ during neuroinflammation. Autophagy and its dysfunction have been implicated in some genetic forms of PD, with alpha-synuclein accumulation and aggregation linked to autophagy suppression. Using alpha-synuclein triplica

Alpha-synuclein (α-syn) is an abundant presynaptic protein that associates with the surface of synaptic vesicles (SVs). It is the main component of Lewy bodies, abnormal protein aggregates that serve as a hallmark of both sporadic and familial forms of Parkinson's disease (PD). While its physiological role in the synapse remains elusive, recent studies indicate it attenuates synaptic transmission and regulates SV clustering. Specifically, when human α-syn (h-α-syn) is over-expressed in mouse neurons by viral transduction or in transgenic mice, it inhibits SV recycling and disperses the SV clus

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder and there is no cure to treat or prevent the disease. The cardinal motor symptoms of PD are caused by a decline of nerve cells producing the neurotransmitter dopamine, which is necessary for the initiation of voluntary movements, but other transmitter systems including the serotonin and norepinephrine systems are affected as well and are related to non-motor symptoms such as depression and dementia. On a pathological level, PD is also characterized by intracellular proteinaceous inclusions known as Lewy bodies that contain t

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons of the Substantia Nigra and the accumulation of protein aggregates, called Lewy bodies, where the most abundant protein is alpha-synuclein (a-SYN). In addition to the neurodegeneration and the accumulation of proteins, PD is characterized by chronic low-grade inflammation and mitochondrial alterations that lead to oxidative stress. Currently, the only treatment for PD patients is dopamine replacement therapy (levodopa), which has serious side effects and does

Parkinson’s disease (PD) is a neurodegenerative process characterized by the presence of Lewy bodies in different brain regions, affection of many neurotransmitter systems and manifestation of motor and nonmotor symptoms. These latter ones often appear before the motor symptomatology and highly impact on the life quality of the patients. Interestingly, the locus coeruleus (LC) that contains the highest density of noradrenergic neurons in the brain, is among the brain stem areas first displaying Lewy bodies in the disease, and is associated with prodromal non-motor symptoms. Despite its small s

Dementia with Lewy Bodies (DLB) is the second most common neurocognitive pathology characterized by pathogenic deposition of α-synuclein-laden Lewy bodies within vulnerable neurons, including those of the hippocampus (HC). The strongest risk factor for sporadic Alzheimer’s disease (AD), and recently demonstrated for DLB, is the ε4 allele of apolipoprotein (APOE4) that is a major lipoprotein in the central nervous system playing a leading role in maintaining lipid homeostasis. Our group recently demonstrated that the APOE4 aggravates cognitive deficits in a mouse model of prodromal DLB – corrob

Although Parkinson's disease (PD) is becoming increasingly important in ageing societies, its diagnosis still relies on the presence of classical motor symptoms that usually manifest in the later stages of the disease's progression. Patients may, however, present non-motor signs as cognitive and/or mood issues years prior to the onset of the motor ones. The Locus Coeruleus (LC) is one of the first areas to exhibit Lewy bodies and neurodegeneration. Its dysfunction is associated to the appearance of nonmotor symptoms due to its noradrenergic (NA) projections and influence on the homeostasis of

Parkinson’s disease (PD) is characterized by the selective loss of dopaminergic neurons in the Substantia Nigra and Lewy body formation, resulting in a progressive neurodegenerative disorder with movement defects. The impairment of dopaminergic innervation in PD hinders the two main projection systems from the dorsal striatum (Putamen, Pu, and Caudate Nucleus, CN) from effectively responding to cortical and thalamic signals.A potential role of Oligodendrocytes (OLs) in PD was pointed out by recent works describing GWAS PD variants associated with OLs (Bryois et al, Nat Genet, 2020), PD genes e

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The disease is mainly characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the abnormal accumulation and aggregation of alpha-synuclein (alpha-syn) in the form of Lewy bodies and Lewy neurites. Even if recent studies allowed for an increased understanding of the role of alpha-syn misfolding and aggregation in PD pathogenesis, many other aspects influence disease onset and progression; among them, evidence suggests neuroinflammation as a key factor of PD casca

Parkinson’s disease (PD) is a progressive disorder of the nervous system, affecting 1% of the ageing population. Common motor symptoms include tremor and bradykinesia, while non-motor symptoms range from constipation to sleep disturbances. The neuropathological hallmarks involve the loss of dopaminergic neurons in the substantia nigra and abnormal intra-neuronal accumulation of Lewy bodies. Here, the zebrafish model is used to investigate the behavioural defects associated with PD. Mutations of PARK2, PINK1, PARK7, LRRK2 and SNCA genes cause different forms of PD in humans. Using CRISPR/Cas9