Increased homocysteine levels correlate with cortical structural damage in Parkinson's disease

In patients with Parkinson’s disease (PD), the molecularly misfolded form of α-synuclein was recently identified in cutaneous autonomic nerve fibers which displayed increased accumulation even in early disease stages. However, the underlying mechanisms of synucleinopathic nerve damage and its implication for brain pathology in later life remain to be elucidated. To date, specific diagnostic tools to evaluate small fiber pathology and to discriminate neurodegenerative proteinopathies are rare. Recently, research has indicated that deposition of α-synuclein in cutaneous nerve fibers quantified via immunohistochemistry in superficial skin biopsies might be a valid marker of PD which could facilitate early diagnosis and monitoring of disease progression. However, lack of standardization of techniques to quantify neural α-synuclein deposition limits their utility in clinical practice. Additional challenges include the identification of potential distinct morphological patterns of intraneural α-synuclein deposition among synucleinopathies to facilitate diagnostic discrimination and determining the degree to which structural damage relates to dysfunction of nerve fibers targeted by α-synuclein. Answering these questions might improve our understanding of the pathophysiological role of small fiber neuropathy in Parkinson’s disease, help identify new treatment targets, and facilitate assessment of response to neuroprotective treatment.

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Circuit imaging biomarkers in preclinical and prodromal Parkinson's disease

Molecular Medicine ◽

10.1186/s10020-021-00327-x ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Sanne K. Meles ◽

Wolfgang H. Oertel ◽

Klaus L. Leenders

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Fdg Pet ◽

Structural Damage ◽

Photon Emission ◽

Disease Process ◽

Nigrostriatal System ◽

Imaging Biomarkers ◽

Emission Computed Tomography ◽

Increased Risk

AbstractParkinson’s disease (PD) commences several years before the onset of motor features. Pathophysiological understanding of the pre-clinical or early prodromal stages of PD are essential for the development of new therapeutic strategies. Two categories of patients are ideal to study the early disease stages. Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents a well-known prodromal stage of PD in which pathology is presumed to have reached the lower brainstem. The majority of patients with iRBD will develop manifest PD within years to decades. Another category encompasses non-manifest mutation carriers, i.e. subjects without symptoms, but with a known mutation or genetic variant which gives an increased risk of developing PD. The speed of progression from preclinical or prodromal to full clinical stages varies among patients and cannot be reliably predicted on the individual level. Clinical trials will require inclusion of patients with a predictable conversion within a limited time window. Biomarkers are necessary that can confirm pre-motor PD status and can provide information regarding lead time and speed of progression. Neuroimaging changes occur early in the disease process and may provide such a biomarker. Studies have focused on radiotracer imaging of the dopaminergic nigrostriatal system, which can be assessed with dopamine transporter (DAT) single photon emission computed tomography (SPECT). Loss of DAT binding represents an effect of irreversible structural damage to the nigrostriatal system. This marker can be used to monitor disease progression and identify individuals at specific risk for phenoconversion. However, it is known that changes in neuronal activity precede structural changes. Functional neuro-imaging techniques, such as 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (18F-FDG PET) and functional magnetic resonance imaging (fMRI), can be used to model the effects of disease on brain networks when combined with advanced analytical methods. Because these changes occur early in the disease process, functional imaging studies are of particular interest in prodromal PD diagnosis. In addition, fMRI and 18F-FDG PET may be able to predict a specific future phenotype in prodromal cohorts, which is not possible with DAT SPECT. The goal of the current review is to discuss the network-level brain changes in pre-motor PD.

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Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-92738-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jing Xie ◽

Shuting Chen ◽

Jean C. Bopassa ◽

Swati Banerjee

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Structural Damage ◽

Neurodegenerative Disorder ◽

Neuronal Loss ◽

In Vivo Studies ◽

Tubulin Polymerization ◽

Protein Mutants ◽

Dopaminergic Neuronal Loss

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder with no known cure. PD is characterized by locomotion deficits, nigrostriatal dopaminergic neuronal loss, mitochondrial dysfunctions and formation of α-Synuclein aggregates. A well-conserved and less understood family of Tubulin Polymerization Promoting Proteins (TPPP) is also implicated in PD and related disorders, where TPPP exists in pathological aggregates in neurons in patient brains. However, there are no in vivo studies on mammalian TPPP to understand the genetics and neuropathology linking TPPP aggregation or neurotoxicity to PD. Recently, we discovered the only Drosophila homolog of human TPPP named Ringmaker (Ringer). Here, we report that adult ringer mutants display progressive locomotor disabilities, reduced lifespan and neurodegeneration. Importantly, our findings reveal that Ringer is associated with mitochondria and ringer mutants have mitochondrial structural damage and dysfunctions. Adult ringer mutants also display progressive loss of dopaminergic neurons. Together, these phenotypes of ringer mutants recapitulate some of the salient features of human PD patients, thus allowing us to utilize ringer mutants as a fly model relevant to PD, and further explore its genetic and molecular underpinnings to gain insights into the role of human TPPP in PD.

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Effects of repetitive transcranial magnetic stimulation on voice and speech in Parkinson's disease

The Journal of Laryngology & Otology ◽

10.1017/s0022215106002787 ◽

2005 ◽

pp. 1

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Repetitive Transcranial Magnetic Stimulation ◽

Voice And Speech

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Emerging Drugs and Targets for Parkinson's Disease

10.1039/9781849737357 ◽

2013 ◽

Cited By ~ 3

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease

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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?

Journal of Speech Language and Hearing Research ◽

10.1044/2020_jslhr-20-00337 ◽

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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