scholarly journals The Benefits of Humanized Yeast Models to Study Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
V. Franssens ◽  
T. Bynens ◽  
J. Van den Brande ◽  
K. Vandermeeren ◽  
M. Verduyckt ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Baker’S Yeast ◽  
Baker's Yeast ◽  
Pathogenic Role ◽  
The Past ◽  
Human Proteins

Over the past decade, the baker’s yeastSaccharomyces cerevisiaehas proven to be a useful model system to investigate fundamental questions concerning the pathogenic role of human proteins in neurodegenerative diseases such as Parkinson’s disease (PD). These so-called humanized yeast models for PD initially focused onα-synuclein, which plays a key role in the etiology of PD. Upon expression of this human protein in the baker’s yeastSaccharomyces cerevisiae, the events leading to aggregation and the molecular mechanisms that result in cellular toxicity are faithfully reproduced. More recently, a similar model to study the presumed pathobiology of theα-synuclein interaction partner synphilin-1 has been established. In this review we will discuss recent advances using these humanized yeast models, pointing to new roles for cell wall integrity signaling, Ca2+homeostasis, mitophagy, and the cytoskeleton.

scholarly journals Pathological Functions of LRRK2 in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2565
Author(s):  
Ga Ram Jeong ◽  
Byoung Dae Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Lewy Bodies ◽  
Gene Encoding ◽  
Pathogenic Mutations ◽  
Abnormal Increase ◽  
Sporadic Parkinson’S Disease ◽  
Lrrk2 Kinase

Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are common genetic risk factors for both familial and sporadic Parkinson’s disease (PD). Pathogenic mutations in LRRK2 have been shown to induce changes in its activity, and abnormal increase in LRRK2 kinase activity is thought to contribute to PD pathology. The precise molecular mechanisms underlying LRRK2-associated PD pathology are far from clear, however the identification of LRRK2 substrates and the elucidation of cellular pathways involved suggest a role of LRRK2 in microtubule dynamics, vesicular trafficking, and synaptic transmission. Moreover, LRRK2 is associated with pathologies of α-synuclein, a major component of Lewy bodies (LBs). Evidence from various cellular and animal models supports a role of LRRK2 in the regulation of aggregation and propagation of α-synuclein. Here, we summarize our current understanding of how pathogenic mutations dysregulate LRRK2 and discuss the possible mechanisms leading to neurodegeneration.

Molecular Interactions of α-Synuclein, Mitochondria, and Cellular Degradation Pathways in Parkinson's Disease

2020 ◽  
pp. 212-234
Author(s):  
Mansi Verma ◽  
Sujata Basu ◽  
Manisha Singh ◽  
Rachana R. ◽  
Simrat Kaur ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Interactions ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Degradation Pathways ◽  
Functional Changes ◽  
The World ◽  
Novel Therapeutic

Parkinson's disease (PD) has been reported to be the most common neurodegenerative diseases all over the world. Several proteins are associated and responsible for causing PD. One such protein is α-synuclein. This chapter discusses the role of α-synuclein in PD. Various genetic and epigenetic factors, which cause structural and functional changes for α-synuclein, have been described. Several molecular mechanisms, which are involved in regulating mitochondrial and lysosomal related pathways and are linked to α-synuclein, have been discussed in detail. The knowledge gathered is further discussed in terms of using α-synuclein as a diagnostic marker for PD and as a novel therapeutic target for the same.

scholarly journals Mitochondrial Fusion/Fission, Transport and Autophagy in Parkinson's Disease: When Mitochondria Get Nasty

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Daniela M. Arduíno ◽  
A. Raquel Esteves ◽  
Sandra M. Cardoso
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Growing Body ◽  
Parkinsonian Disorders ◽  
Mitochondrial Trafficking

Understanding the molecular basis of Parkinson's disease (PD) has proven to be a major challenge in the field of neurodegenerative diseases. Although several hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of PD, a growing body of evidence has highlighted the role of mitochondrial dysfunction and the disruption of the mechanisms of mitochondrial dynamics in PD and other parkinsonian disorders. In this paper, we comment on the recent advances in how changes in the mitochondrial function and mitochondrial dynamics (fusion/fission, transport, and clearance) contribute to neurodegeneration, specifically focusing on PD. We also evaluate the current controversies in those issues and discuss the role of fusion/fission dynamics in the mitochondrial lifecycle and maintenance. We propose that cellular demise and neurodegeneration in PD are due to the interplay between mitochondrial dysfunction, mitochondrial trafficking disruption, and impaired autophagic clearance.

scholarly journals Neuron-Astrocyte Interactions in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2623
Author(s):  
Ikuko Miyazaki ◽  
Masato Asanuma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Therapeutic Strategies ◽  
Pathogenic Role ◽  
Waste Products ◽  
Disease Modifying Drugs ◽  
Dopaminergic Neurodegeneration ◽  
The Central Nervous System

Parkinson’s disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus on the involvement of non-neuronal cells in the progression of PD pathology. Astrocytes are the most numerous glial cells in the central nervous system. Normally, astrocytes protect neurons by releasing neurotrophic factors, producing antioxidants, and disposing of neuronal waste products. However, in pathological situations, astrocytes are known to produce inflammatory cytokines. In addition, various studies have reported that astrocyte dysfunction also leads to neurodegeneration in PD. In this article, we summarize the interaction of astrocytes and dopaminergic neurons, review the pathogenic role of astrocytes in PD, and discuss therapeutic strategies for the prevention of dopaminergic neurodegeneration. This review highlights neuron-astrocyte interaction as a target for the development of disease-modifying drugs for PD in the future.

Role of α-synuclein in neurodegeneration: implications for the pathogenesis of Parkinson's disease

2014 ◽  
Vol 56 ◽  
pp. 125-135 ◽  
Author(s):  
Shun Yu ◽  
Piu Chan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Experimental Studies ◽  
Research Progress ◽  
Pathogenic Role ◽  
Normal Expression ◽  
The Brain ◽  
Recent Research Progress

α-Syn (α-synuclein) is a small soluble acidic protein that is extensively expressed in the nervous system. Genetic, clinical and experimental studies demonstrate that α-syn is strongly implicated in the pathogenesis of PD (Parkinson's disease). However, the pathogenic mechanism remains elusive. In the present chapter, we first describe the normal expression and potential physiological functions of α-syn. Then, we introduce recent research progress related to the pathogenic role of α-syn in PD, with special emphasis on how α-syn oligomers cause the preferential degeneration of dopaminergic neurons in the substantia nigra and the spreading of α-syn pathology in the brain of PD patients.

scholarly journals Non-Conventional Yeasts as Alternatives in Modern Baking for Improved Performance and Aroma Enhancement

Fermentation ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 102
Author(s):  
Nerve Zhou ◽  
Thandiwe Semumu ◽  
Amparo Gamero
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Stress Tolerance ◽  
Baker’S Yeast ◽  
Baker's Yeast ◽  
Principal Role ◽  
Yeast Strains ◽  
Improved Performance ◽  
Baking Industry ◽  
Cereal Flour

Saccharomyces cerevisiae remains the baker’s yeast of choice in the baking industry. However, its ability to ferment cereal flour sugars and accumulate CO2 as a principal role of yeast in baking is not as unique as previously thought decades ago. The widely conserved fermentative lifestyle among the Saccharomycotina has increased our interest in the search for non-conventional yeast strains to either augment conventional baker’s yeast or develop robust strains to cater for the now diverse consumer-driven markets. A decade of research on alternative baker’s yeasts has shown that non-conventional yeasts are increasingly becoming important due to their wide carbon fermentation ranges, their novel aromatic flavour generation, and their robust stress tolerance. This review presents the credentials of non-conventional yeasts as attractive yeasts for modern baking. The evolution of the fermentative trait and tolerance to baking-associated stresses as two important attributes of baker’s yeast are discussed besides their contribution to aroma enhancement. The review further discusses the approaches to obtain new strains suitable for baking applications.

Stratification Strategies for Patients to Optimize the Effectiveness of Scavenging Biogenic Aldehydes: Towards a Neuroprotective Approach for Parkinson’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Anna Masato ◽  
Michele Sandre ◽  
Angelo Antonini ◽  
Luigi Bubacco
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Primary Amines ◽  
Regulatory Processes ◽  
Reactive Aldehydes ◽  
Glycation End Products ◽  
Lysine Residues ◽  
The Brain

Parkinson’s disease (PD) is a clinically heterogeneous disorder with a multi-factorial pathology. Various molecular mechanisms are involved in the pathogenesis of PD, converging to oxidative stress and proteinopathy. The accumulation of reactive aldehydes (i.e., the dopamine metabolite DOPAL, lipid-peroxidation products, and advanced glycation end-products) has been reported in PD patients’ brains. Aldehydes easily react with primary amines such as lysine residues, which are involved in several regulatory processes in cells. Therefore, aldehyde adducts lead to severe consequences, including neuronal proteostasis, mitochondrial dysfunction, and cell death. In this review, we analyzed the scavenging role of amines toward toxic aldehydes in the brain. Interestingly, small molecules like metformin, rasagiline, hydralazine are already clinically available and used in the therapy for PD and other diseases. Hence, we propose to reevaluate this class of drugs as a disease-modifiers for PD, and we suggest that improved analysis of their pharmacology and bioavailability in the brain, together with a more precise patients stratification, should be considered before planning future clinical trials.

scholarly journals Dopamine Oxidation and Autophagy

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Patricia Muñoz ◽  
Sandro Huenchuguala ◽  
Irmgard Paris ◽  
Juan Segura-Aguilar
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Protein Degradation ◽  
Dopaminergic Neurons ◽  
Molecular Mechanisms ◽  
Neurodegenerative Process ◽  
Dopamine Oxidation

The molecular mechanisms involved in the neurodegenerative process of Parkinson's disease remain unclear. Currently, there is a general agreement that mitochondrial dysfunction,α-synuclein aggregation, oxidative stress, neuroinflammation, and impaired protein degradation are involved in the neurodegeneration of dopaminergic neurons containing neuromelanin in Parkinson's disease. Aminochrome has been proposed to play an essential role in the degeneration of dopaminergic neurons containing neuromelanin by inducing mitochondrial dysfunction, oxidative stress, the formation of neurotoxicα-synuclein protofibrils, and impaired protein degradation. Here, we discuss the relationship between the oxidation of dopamine to aminochrome, the precursor of neuromelanin, autophagy dysfunction in dopaminergic neurons containing neuromelanin, and the role of dopamine oxidation to aminochrome in autophagy dysfunction in dopaminergic neurons. Aminochrome induces the following: (i) the formation ofα-synuclein protofibrils that inactivate chaperone-mediated autophagy; (ii) the formation of adducts withα- andβ-tubulin, which induce the aggregation of the microtubules required for the fusion of autophagy vacuoles and lysosomes.

scholarly journals Parkinson’s Disease-Related Genes and Lipid Alteration

2021 ◽  
Vol 22 (14) ◽  
pp. 7630
Author(s):  
Milena Fais ◽  
Antonio Dore ◽  
Manuela Galioto ◽  
Grazia Galleri ◽  
Claudia Crosio ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Clinical Manifestations ◽  
Alpha Synuclein ◽  
Experimental Models ◽  
Protein Clearance ◽  
Genetic And Environmental Factors

Parkinson’s disease (PD) is a complex and progressive neurodegenerative disorder with a prevalence of approximately 0.5–1% among those aged 65–70 years. Although most of its clinical manifestations are due to a loss of dopaminergic neurons, the PD etiology is largely unknown. PD is caused by a combination of genetic and environmental factors, and the exact interplay between genes and the environment is still debated. Several biological processes have been implicated in PD, including mitochondrial or lysosomal dysfunctions, alteration in protein clearance, and neuroinflammation, but a common molecular mechanism connecting the different cellular alterations remains incompletely understood. Accumulating evidence underlines a significant role of lipids in the pathological pathways leading to PD. Beside the well-described lipid alteration in idiopathic PD, this review summarizes the several lipid alterations observed in experimental models expressing PD-related genes and suggests a possible scenario in relationship to the molecular mechanisms of neuronal toxicity. PD could be considered a lipid-induced proteinopathy, where alteration in lipid composition or metabolism could induce protein alteration—for instance, alpha-synuclein accumulation—and finally neuronal death.

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