scholarly journals Lysosomal function in macromolecular homeostasis and bioenergetics in Parkinson's disease

2010 ◽  
Vol 5 (1) ◽  
pp. 14 ◽  
Author(s):  
Lonnie Schneider ◽  
Jianhua Zhang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lysosomal Function

scholarly journals Endo-lysosomal proteins and ubiquitin CSF concentrations in Alzheimer’s and Parkinson’s disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Simon Sjödin ◽  
Gunnar Brinkmalm ◽  
Annika Öhrfelt ◽  
Lucilla Parnetti ◽  
Silvia Paciotti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Solid Phase ◽  
Ubiquitin Proteasome System ◽  
Cross Sectional ◽  
Lysosomal Function ◽  
Lysosomal Disorders ◽  
Prodromal Ad ◽  
Genes Encoding ◽  
Ubiquitin Proteasome

Abstract Background Increasing evidence implicates dysfunctional proteostasis and the involvement of the autophagic and endo-lysosomal system and the ubiquitin-proteasome system in neurodegenerative diseases. In Alzheimer’s disease (AD), there is an accumulation of autophagic vacuoles within the neurons. In Parkinson’s disease (PD), susceptibility has been linked to genes encoding proteins involved in autophagy and lysosomal function, as well as mutations causing lysosomal disorders. Furthermore, both diseases are characterized by the accumulation of protein aggregates. Methods Proteins associated with endocytosis, lysosomal function, and the ubiquitin-proteasome system were identified in the cerebrospinal fluid (CSF) and targeted by combining solid-phase extraction and parallel reaction monitoring mass spectrometry. In total, 50 peptides from 18 proteins were quantified in three cross-sectional cohorts including AD (N = 61), PD (N = 21), prodromal AD (N = 10), stable mild cognitive impairment (N = 15), and controls (N = 68). Results A pilot study, including subjects selected based on their AD CSF core biomarker concentrations, showed increased concentrations of several targeted proteins in subjects with core biomarker levels indicating AD pathology compared to controls. Next, in a clinically characterized cohort, lower concentrations in CSF of proteins in PD were found compared to subjects with prodromal AD. Further investigation in an additional clinical study again revealed lower concentrations in CSF of proteins in PD compared to controls and AD. Conclusion In summary, significantly different peptide CSF concentrations were identified from proteins AP2B1, C9, CTSB, CTSF, GM2A, LAMP1, LAMP2, TCN2, and ubiquitin. Proteins found to have altered concentrations in more than one study were AP2B1, CTSB, CTSF, GM2A, LAMP2, and ubiquitin. Interestingly, given the genetic implication of lysosomal function in PD, we did identify the CSF concentrations of CTSB, CTSF, GM2A, and LAMP2 to be altered. However, we also found differences in proteins associated with endocytosis (AP2B1) and the ubiquitin-proteasome system (ubiquitin). No difference in any peptide CSF concentration was found in clinically characterized subjects with AD compared to controls. In conclusion, CSF analyses of subjects with PD suggest a general lysosomal dysfunction, which resonates well with recent genetic findings, while such changes are minor or absent in AD.

The function of lysosomes and their role in Parkinson’s disease

Neuroforum ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 43-51
Author(s):  
Friederike Zunke
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lysosomal Storage ◽  
Lysosomal Function ◽  
Potential Risk Factors ◽  
Lysosomal Membrane Proteins ◽  
Novel Therapeutic Strategies ◽  
Turn Over ◽  
Soluble Enzymes ◽  
Cellular Organelles

AbstractLysosomes are cellular organelles that are important for the degradation and recycling of various biomolecules. Specialized lysosomal membrane proteins, as well as soluble enzymes, are important for the efficient turn-over of lysosomal substrates. A deficiency in the degradative capacity of lysosomes leads to severe pathologies referred to as lysosomal storage disorders. There is increasing evidence for the importance of lysosomal function in neurodegenerative disorders, including Parkinson’s disease. One reason for this might be the vulnerability of neuronal cells. Since neurons do not undergo further cell division, non-degraded substrates accumulate in aging cells, causing a buildup of toxicity. Recent genomic screenings identified a number of lysosome-associated genes as potential risk factors for Parkinson’s disease, which are discussed in this review. Moreover, it is outlined how targeting lysosomal function might help in developing novel therapeutic strategies.

Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease

2015 ◽  
Vol 18 (6) ◽  
pp. 826-835 ◽  
Author(s):  
Ariadna Laguna ◽  
Nicoletta Schintu ◽  
André Nobre ◽  
Alexandra Alvarsson ◽  
Nikolaos Volakakis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lysosomal Function ◽  
Dopaminergic Control

scholarly journals The Emerging Role of the Lysosome in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2399
Author(s):  
Alba Navarro-Romero ◽  
Marta Montpeyó ◽  
Marta Martinez-Vicente
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Risk ◽  
Lysosomal Storage Diseases ◽  
Genetic Risk Factors ◽  
Brain Regions ◽  
Lysosomal Storage ◽  
Lysosomal Function ◽  
Lysosomal Dysfunction

Lysosomal function has a central role in maintaining neuronal homeostasis, and, accordingly, lysosomal dysfunction has been linked to neurodegeneration and particularly to Parkinson’s disease (PD). Lysosomes are the converging step where the substrates delivered by autophagy and endocytosis are degraded in order to recycle their primary components to rebuild new macromolecules. Genetic studies have revealed the important link between the lysosomal function and PD; several of the autosomal dominant and recessive genes associated with PD as well as several genetic risk factors encode for lysosomal, autophagic, and endosomal proteins. Mutations in these PD-associated genes can cause lysosomal dysfunction, and since α-synuclein degradation is mostly lysosomal-dependent, among other consequences, lysosomal impairment can affect α-synuclein turnover, contributing to increase its intracellular levels and therefore promoting its accumulation and aggregation. Recent studies have also highlighted the bidirectional link between Parkinson’s disease and lysosomal storage diseases (LSD); evidence includes the presence of α-synuclein inclusions in the brain regions of patients with LSD and the identification of several lysosomal genes involved in LSD as genetic risk factors to develop PD.

scholarly journals Potential Tear Biomarkers for the Diagnosis of Parkinson’s Disease—A Pilot Study

Proteomes ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 4
Author(s):  
Arantxa Acera ◽  
Juan Carlos Gómez-Esteban ◽  
Ane Murueta-Goyena ◽  
Marta Galdos ◽  
Mikel Azkargorta ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pilot Study ◽  
Neurological Impairment ◽  
Lysosomal Function ◽  
Tear Proteins ◽  
Proteomic Data ◽  
Healthy Control ◽  
Nano Liquid Chromatography ◽  
Proteome Profile

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. In this study, the tear proteome profile of patients with idiopathic PD (iPD, n = 24), carriers of the E46K-SNCA mutation (n = 3) and healthy control (CT, n = 27) subjects was analyzed to identify candidate biomarkers for the diagnosis of PD. An observational, prospective and case-control pilot study was carried out, analyzing the participants tear samples by nano-liquid chromatography–mass spectrometry (nLC–MS/MS) and assessing their neurological impairment. The proteomic data obtained are available at ProteomeXchange with identifier 10.6019/PXD028811. These analyses led to the identification of 560 tear proteins, some of which were deregulated in PD patients and that have been implicated in immune responses, inflammation, apoptosis, collagen degradation, protein synthesis, defense, lipid transport and altered lysosomal function. Of these proteins, six were related to neurodegenerative processes and showed a good capacity to classify patients and controls. These findings revealed that certain proteins were upregulated in the tears of PD patients, mainly proteins involved in lysosomal function. Thus, in this study, tear proteins were identified that are implicated in neurodegeneration and that may be related to an aggressive disease phenotype in PD patients.

Evaluation of Efferent Auditory System and Hearing Quality in Parkinson's Disease: Is the Difficulty in Speech Understanding in Complex Listening Conditions Related to Neural Degeneration or Aging?

2020 ◽  
pp. 1-9
Author(s):  
Nuriye Yıldırım Gökay ◽  
Bülent Gündüz ◽  
Fatih Söke ◽  
Recep Karamert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Auditory System ◽  
Otoacoustic Emissions ◽  
Pure Tone ◽  
Pure Tone Audiometry ◽  
Auditory Pathway ◽  
Normal Hearing ◽  
System Function ◽  
Distortion Product

Purpose The effects of neurological diseases on the auditory system have been a notable issue for investigators because the auditory pathway is closely associated with neural systems. The purposes of this study are to evaluate the efferent auditory system function and hearing quality in Parkinson's disease (PD) and to compare the findings with age-matched individuals without PD to present a perspective on aging. Method The study included 35 individuals with PD (mean age of 48.50 ± 8.00 years) and 35 normal-hearing peers (mean age of 49 ± 10 years). The following tests were administered for all participants: the first section of the Speech, Spatial and Qualities of Hearing Scale; pure-tone audiometry, speech audiometry, tympanometry, and acoustic reflexes; and distortion product otoacoustic emissions (DPOAEs) and contralateral suppression of DPOAEs. SPSS Version 25 was used for statistical analyses, and values of p < .05 were considered statistically significant. Results There were no statistically significant differences in the pure-tone audiometry thresholds and DPOAE responses between the individuals with PD and their normal-hearing peers ( p = .732). However, statistically significant differences were found between the groups in suppression levels of DPOAEs and hearing quality ( p < .05). In addition, a statistically significant and positive correlation was found between the amount of suppression at some frequencies and the Speech, Spatial and Qualities of Hearing Scale scores. Conclusions This study indicates that medial olivocochlear efferent system function and the hearing quality of individuals with PD were affected adversely due to the results of PD pathophysiology on the hearing system. For optimal intervention and follow-up, tasks related to hearing quality in daily life can also be added to therapies for PD.

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