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Pathological Correlates of Cognitive Decline in Parkinson’s Disease: From Molecules to Neural Networks

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Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the death of dopaminergic neurons in the substantia nigra and appearance of protein aggregates (Lewy bodies) consisting predominantly of α-synuclein in neurons. PD is currently recognized as a multisystem disorder characterized by severe motor impairments and various non-motor symptoms. Cognitive decline is one of the most common and worrisome non-motor symptoms. Moderate cognitive impairments (CI) are diagnosed already at the early stages of PD, usually transform into dementia. The main types of CI in PD include executive dysfunction, attention and memory decline, visuospatial impairments, and verbal deficits. According to the published data, the following mechanisms play an essential role demonstrates a crucial importance in the decline of the motor and cognitive functions in PD: (1) changes in the conformational structure of transsynaptic proteins and protein aggregation in presynapses; (2) synaptic transmission impairment; (3) neuroinflammation (pathological activation of the neuroglia); (4) mitochondrial dysfunction and oxidative stress; (5) metabolic disorders (hypometabolism of glucose, dysfunction of glycolipid metabolism; and (6) functional rearrangement of neuronal networks. These changes can lead to the death of dopaminergic cells in the substantia nigra and affect the functioning of other neurotransmitter systems, thus disturbing neuronal networks involved in the transmission of information related to the regulation of motor activity and cognitive functions. Identification of factors causing detrimental changes in PD and methods for their elimination will help in the development of new approaches to the therapy of PD. The goal of this review was to analyze pathological processes that take place in the brain and underlie the onset of cognitive disorders in PD, as well as to describe the impairments of cognitive functions in this disease.

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Abbreviations

6-OHDA:

6-hydroxydopamine

αSyn:

α-synuclein

AD:

Alzheimer’s disease

CI:

cognitive impairment

CSF:

cerebrospinal fluid

FC:

functional connectivity

fMRI:

functional magnetic resonance imaging

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PET:

positron emission tomography

PD:

Parkinson’s disease

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Funding

The work was performed within the framework of state assignment no. 075-01025-23-01.

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Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Nikolai I. Novikov, Elena S. Brazhnik & Valentina F. Kitchigina

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  1. Nikolai I. Novikov
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  2. Elena S. Brazhnik
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  3. Valentina F. Kitchigina
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V.F.K. proposed the idea and edited the manuscript. All authors contributed equally to the article.

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Correspondence to Valentina F. Kitchigina.

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The authors declare no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Novikov, N.I., Brazhnik, E.S. & Kitchigina, V.F. Pathological Correlates of Cognitive Decline in Parkinson’s Disease: From Molecules to Neural Networks. Biochemistry Moscow 88, 1890–1904 (2023). https://doi.org/10.1134/S0006297923110172

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  • DOI: https://doi.org/10.1134/S0006297923110172

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