Neuro-Immunity and Gut Dysbiosis Drive Parkinson’s Disease-Induced Pain

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 1–2% of the population aged 65 and over. Additionally, non-motor symptoms such as pain and gastrointestinal dysregulation are also common in PD. These impairments might stem from a dysregulation within the gut-brain axis that alters immunity and the inflammatory state and subsequently drives neurodegeneration. There is increasing evidence linking gut dysbiosis to the severity of PD’s motor symptoms as well as to somatosensory hypersensitivities. Altogether, these interdependent features highlight the urgency of reviewing the links between the onset of PD’s non-motor symptoms and gut immunity and whether such interplays drive the progression of PD. This review will shed light on maladaptive neuro-immune crosstalk in the context of gut dysbiosis and will posit that such deleterious interplays lead to PD-induced pain hypersensitivity.

Alpha-Synuclein and Cognitive Decline in Parkinson Disease

Parkinson disease (PD) is the second most common neurodegenerative disorder in elderly people. It is characterized by the aggregation of misfolded alpha-synuclein throughout the nervous system. Aside from cardinal motor symptoms, cognitive impairment is one of the most disabling non-motor symptoms that occurs during the progression of the disease. The accumulation and spreading of alpha-synuclein pathology from the brainstem to limbic and neocortical structures is correlated with emerging cognitive decline in PD. This review summarizes the genetic and pathophysiologic relationship between alpha-synuclein and cognitive impairment in PD, together with potential areas of biomarker advancement.

Astrocyte dysfunction in Parkinson's disease: from the perspectives of transmitted α-synuclein and genetic modulation

Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily affects the elderly. While the etiology of PD is likely multifactorial with the involvement of genetic, environmental, aging and other factors, α-synuclein (α-syn) pathology is a pivotal mechanism underlying the development of PD. In recent years, astrocytes have attracted considerable attention in the field. Although astrocytes perform a variety of physiological functions in the brain, they are pivotal mediators of α-syn toxicity since they internalize α-syn released from damaged neurons, and this triggers an inflammatory response, protein degradation dysfunction, mitochondrial dysfunction and endoplasmic reticulum stress. Astrocytes are indispensable coordinators in the background of several genetic mutations, including PARK7, GBA1, LRRK2, ATP13A2, PINK1, PRKN and PLA2G6. As the most abundant glial cells in the brain, functional astrocytes can be replenished and even converted to functional neurons. In this review, we discuss astrocyte dysfunction in PD with an emphasis on α-syn toxicity and genetic modulation and conclude that astrocyte replenishment is a valuable therapeutic approach in PD.

Review of medicine utilization for Parkinson’s disease management: the Bulgarian perspective

Background: Parkinson’s disease (PD), which occurs in 1% of the population, is the second most common neurodegenerative disorder. Despite the broad spectrum of PD manifestations and high disease prevalence, there are insufficient data on medicine utilization and prescription strategies. The purpose of the current study was to analyze published data concerning treatment approaches and to compare them with Bulgarian therapeutic practice.Design and methods: We conducted a systematic review of the PubMed and Google Scholar databases, and we calculated medicine utilization in Bulgaria during 2018 and 2019 using the WHO methodology.Results: The literature search identified a total of 311 publications, but only 12 met the inclusion criteria. Eleven studies pointed out that levodopa-containing medicine are the most frequently used, followed by dopamine agonists. The highest rate was found for levodopa-containing products and decarboxylase inhibitor (1.06 and 1.33 DDD/1000 inh/day), followed by anticholinergic Biperiden (0.494 and 0.455 DDD/1000 inh/day) during 2018 and 2019 in Bulgaria.Conclusion: Overall, the treatment approaches used in the last decade comply with guideline recommendations, despite variations in levodopa and dopamine agonist utilization. Even though new medicines have been approved for PD management, levodopa-containing products are still most often prescribed and used worldwide.

Roles of Non-Coding RNAs as Novel Diagnostic Biomarkers in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 5%of the elderly population. Currently, the diagnosis of PD is mainly based on clinical features and no definitive diagnostic biomarkers have been identified. The discovery of biomarkers at the earliest stages of PD is of extreme interest. This review focuses on the current findings in the field of circulating non-coding RNAs in PD. We briefly describe the more established circulating biomarkers in PD and provide a more thorough review of non-coding RNAs, in particular microRNAs, long non-coding RNAs and circular RNAs, differentially expressed in PD, highlighting their potential for being considered as biomarkers for diagnosis. Together, these studies hold promise for the use of peripheral biomarkers for the diagnosis of PD.

Parkinson's Disease Genetics and Pathophysiology

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in Lewy bodies. PD is caused by a combination of environmental factors and genetic variants. These variants range from highly penetrant Mendelian alleles to alleles that only modestly increase disease risk. Here, we review what is known about the genetics of PD. We also describe how PD genetics have solidified the role of endosomal, lysosomal, and mitochondrial dysfunction in PD pathophysiology. Finally, we highlight how all three pathways are affected by α-synuclein and how this knowledge may be harnessed for the development of disease-modifying therapeutics.

Dysfunction of Synaptic Vesicle Endocytosis in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. It is a chronic and progressive disorder estimated to affect at least 4 million people worldwide. Although the etiology of PD remains unclear, it has been found that the dysfunction of synaptic vesicle endocytosis (SVE) in neural terminal happens before the loss of dopaminergic neurons. Recently, accumulating evidence reveals that the PD-linked synaptic genes, including DNAJC6, SYNJ1, and SH3GL2, significantly contribute to the disruptions of SVE, which is vital for the pathogenesis of PD. In addition, the proteins encoded by other PD-associated genes such as SNCA, LRRK2, PRKN, and DJ-1 also play key roles in the regulation of SVE. Here we present the facts about SVE-related genes and discussed their potential relevance to the pathogenesis of PD.

The fluid biomarkers of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. However, it still has no available disease‐modifying therapies. Its pathology cascade begins decades before symptomatic presentation. For these reasons, highly sensitive and highly specific fluid biomarkers should be developed for the early diagnosis of AD. In this study, the well‐established and emerging fluid biomarkers of AD are summarized, and recent advances on their role in early diagnosis and progression monitoring as well as their correlations with AD pathology are highlighted. Future prospects and related research directions are also discussed.

Targeted Graphene Oxide for Drug Delivery as a Therapeutic Nanoplatform against Parkinson’s Disease

There has been an exponential increase in the rate of incidence of Parkinson’s disease (PD) with the aging of the global population. PD, the second most common neurodegenerative disorder, results...

THE MOTOR SYMPTOMS–CHALLENGE IN DIAGNOSIS OF PARKINSON'S DISEASE

Parkinson's disease (PD) is the second most common neurodegenerative disorder after the dementia of Alzheimer. The clinical presentation of PD is dominated by typical motor symptoms as resting tremor, cogwheel rigidity, bradykinesia, and postural instability. Non-motor symptoms (NMS) of Parkinson's disease are common but are often under-recognized in clinical practice either due to the lack of spontaneous complaints by the patients or to the absence of systematic questioning by healthcare professionals. In contrast to motor dysfunctions, non-motor symptoms frequently remain unreported. Recently, a self-completed NMS questionnaire and NMS scale for identification and evaluation of these symptoms have been validated. An international survey has shown that up to 62% of NMS in PD remain undeclared to healthcare professionals because patients are unaware that NMS symptoms are linked to PD. Based on both clinical and neuropathological data, PD, traditionally accepted as a dopaminergic motor disorder, now can be characterized as a multisystem neurodegenerative disease that involves many neurotransmitter systems and affects not only motor but non-motor functions, too.