Role of increased levels of endothelial factors in cognitive impairment in the Parkinson’s disease and vascular parkinsonism

2019 ◽  
Vol 405 ◽  
pp. 288-289
Author(s):  
D. Akramova ◽  
G. Rakhimbaeva
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Vascular Parkinsonism ◽  
Endothelial Factors

scholarly journals The Role of NOX4 in Parkinson’s Disease with Dementia

2019 ◽  
Vol 20 (3) ◽  
pp. 696 ◽  
Author(s):  
Dong-Hee Choi ◽  
In-Ae Choi ◽  
Cheol Lee ◽  
Ji Yun ◽  
Jongmin Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Alpha Synuclein ◽  
Cognitive Status ◽  
Dopamine Neurons ◽  
Parkinson’S Disease With Dementia ◽  
6 Hydroxydopamine ◽  
Nigrostriatal Dopamine Neurons

The neuropathology of Parkinson’s disease with dementia (PDD) has been reported to involve heterogeneous and various disease mechanisms. Alpha-synuclein (α-syn) and amyloid beta (Aβ) pathology are associated with the cognitive status of PDD, and NADPH oxidase (NOX) is known to affect a variety of cognitive functions. We investigated the effects of NOX on cognitive impairment and on α-syn and Aβ expression and aggregation in PDD. In the 6-hydroxydopamine (6-OHDA)-injected mouse model, cognitive and motor function, and the levels of α-syn, Aβ, and oligomer A11 after inhibition of NOX4 expression in the hippocampal dentate gyrus (DG) were measured by the Morris water maze, novel object recognition, rotation, and rotarod tests, as well as immunoblotting and immunohistochemistry. After 6-OHDA administration, the death of nigrostriatal dopamine neurons and the expression of α-syn and NOX1 in the substantia nigra were increased, and phosphorylated α-syn, Aβ, oligomer A11, and NOX4 were upregulated in the hippocampus. 6-OHDA dose-dependent cognitive impairment was observed, and the increased cognitive impairment, Aβ expression, and oligomer A11 production in 6-OHDA-treated mice were suppressed by NOX4 knockdown in the hippocampal DG. Our results suggest that increased expression of NOX4 in the hippocampal DG in the 6-OHDA-treated mouse induces Aβ expression and oligomer A11 production, thereby reducing cognitive function.

scholarly journals The Role of Lysosomes in a Broad Disease-Modifying Approach Evaluated across Transgenic Mouse Models of Alzheimer’s Disease and Parkinson’s Disease and Models of Mild Cognitive Impairment

2019 ◽  
Vol 20 (18) ◽  
pp. 4432 ◽  
Author(s):  
Jeannie Hwang ◽  
Candice M. Estick ◽  
Uzoma S. Ikonne ◽  
David Butler ◽  
Morgan C. Pait ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Age Related ◽  
Disease Modifying

Many neurodegenerative disorders have lysosomal impediments, and the list of proposed treatments targeting lysosomes is growing. We investigated the role of lysosomes in Alzheimer’s disease (AD) and other age-related disorders, as well as in a strategy to compensate for lysosomal disturbances. Comprehensive immunostaining was used to analyze brains from wild-type mice vs. amyloid precursor protein/presenilin-1 (APP/PS1) mice that express mutant proteins linked to familial AD. Also, lysosomal modulation was evaluated for inducing synaptic and behavioral improvements in transgenic models of AD and Parkinson’s disease, and in models of mild cognitive impairment (MCI). Amyloid plaques were surrounded by swollen organelles positive for the lysosome-associated membrane protein 1 (LAMP1) in the APP/PS1 cortex and hippocampus, regions with robust synaptic deterioration. Within neurons, lysosomes contain the amyloid β 42 (Aβ42) degradation product Aβ38, and this indicator of Aβ42 detoxification was augmented by Z-Phe-Ala-diazomethylketone (PADK; also known as ZFAD) as it enhanced the lysosomal hydrolase cathepsin B (CatB). PADK promoted Aβ42 colocalization with CatB in lysosomes that formed clusters in neurons, while reducing Aβ deposits as well. PADK also reduced amyloidogenic peptides and α-synuclein in correspondence with restored synaptic markers, and both synaptic and cognitive measures were improved in the APP/PS1 and MCI models. These findings indicate that lysosomal perturbation contributes to synaptic and cognitive decay, whereas safely enhancing protein clearance through modulated CatB ameliorates the compromised synapses and cognition, thus supporting early CatB upregulation as a disease-modifying therapy that may also slow the MCI to dementia continuum.

scholarly journals Neurochemical Basis of Dementia in Parkinson’s Disease

1984 ◽  
Vol 11 (S1) ◽  
pp. 185-190 ◽  
Author(s):  
Oleh Hornykiewicz ◽  
Stephen J. Kish
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Brain Pathology ◽  
Alzheimer Type ◽  
Alzheimer Type Dementia ◽  
Neuron Function ◽  
Additional Role ◽  
Choline Acetyltransferase Activity

ABSTRACTAccording to their mental status, patients with Parkinson’s disease can be subdivided into three groups: (1) mentally normal patients; (2) patients with severe cognitive impairment and Alzheimer-type brain pathology (neuritic plaques, neurofibrillary tangles, granulovacuolar changes); and (3) demented patients without any evidence of Alzheimer changes. Neurochemically, irrespective of the presence or absence of Alzheimer-type brain pathology, demented Parkinson patients seem to have the same disturbance of cortical cholinergic neuron function as patients with Alzheimer-type dementia (Alzheimer’s disease), namely, reduced levels of cortical acetylcholine esterase and choline acetyltransferase activity. At present, the question whether the “cortical cholinergic deficiency” is the only (or sufficient) neurochemical basis for the cognitive impairment in Parkinson patients with dementia cannot be answered with certainty; the additional role of other neurotransmitter changes known to occur in the Parkinson brain, especially loss of cortical, hippocampal and subcortical noradrenaline and/or dopamine cannot be ruled out.

Role of G-protein coupled receptor kinase 5 gene in cognitive impairment in Parkinson's disease

2015 ◽  
Vol 230 (3) ◽  
pp. 975-977 ◽  
Author(s):  
Giuseppe Nicoletti ◽  
Vincenzo De Luca ◽  
Patrizia Tarantino ◽  
Monica Gagliardi ◽  
Grazia Iannello ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
G Protein ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Mild Cognitive Impairment in Parkinson’s Disease: A Review of Current Concepts

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Natalie C. Palavra ◽  
Sharon L. Naismith ◽  
Simon J. G. Lewis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Recognition ◽  
Treatment Options ◽  
Screening Tools ◽  
Therapeutic Interventions

Mild Cognitive Impairment in Parkinson’s Disease (PD-MCI) is common and may be associated with accelerated progression to dementia. Considering the importance of this emerging entity, new diagnostic criteria have recently been proposed. Early recognition and accurate classification of PD-MCI could offer opportunities for novel therapeutic interventions. This review discusses current definitions for PD-MCI, the screening tools used, the pattern of cognitive deficits observed, and the predictors of cognitive decline and transition to Parkinson’s Disease Dementia. Emerging biomarkers, which may aid diagnosis, are also explored and the role of novel treatment options is considered.

Sign in / Sign up

Export Citation Format

Share Document