المؤلفون: Sandra M. Cardoso, A. Raquel Esteves

المصدر: The Neuroscientist. 23:16-26

مصطلحات موضوعية: 0301 basic medicine, Parkinson's disease, Kinase, General Neuroscience, Autophagy, Biology, Mitochondrion, medicine.disease, LRRK2, nervous system diseases, Cell biology, 03 medical and health sciences, Cytosol, 030104 developmental biology, 0302 clinical medicine, Microtubule, medicine, Neurology (clinical), Cytoskeleton, 030217 neurology & neurosurgery

الوصف: Mutations in leucine-rich repeat kinase 2 ( lrrk2) gene cause inherited Parkinson’s disease (PD), and common variants in lrrk2 are a risk factor for sporadic PD. The neuropathology associated with LRRK2-linked PD is extremely pleomorphic involving inclusions of α-synuclein (SNCA), tau or neither, therefore suggesting that LRRK2 may be central in the pathogenic pathways of PD. This large protein localizes in the cytosol, as well as, in specific membrane domains, including mitochondria and autophagosomes and interacts with a wide range of proteins such as SNCA, tau, α- and β-tubulin. For this reason LRRK2 has been associated with a variety of cellular functions, including autophagy, mitochondrial function/dynamics and microtubule/cytoskeletal dynamics. LRRK2 has been shown to interact with microtubules as well as with mitochondria interfering with their network and dynamics. Moreover, LRRK2 knock-out or mutations affect autophagic efficiency. Here, we review and discuss the literature on how LRRK2 affects mitochondrial function, autophagy, and microtubule dynamics and how this is implicated in the PD etiology.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8aa131871058bb438432be387715f04dTest
https://doi.org/10.1177/1073858415616558Test

المؤلفون: Tania Marcourakis, Rodrigo S. Chaves, Karla P. Melo, Michael F. Almeida, Carolliny M. Silva, Sandra M. Cardoso, Marilene Demasi, Luis Eduardo Soares Netto, Merari F. R. Ferrari

المصدر: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP

مصطلحات موضوعية: 0301 basic medicine, Male, medicine.medical_specialty, Insecticides, Physical exercise, Toxicology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Physical Conditioning, Animal, Rotenone, medicine, Animals, ESTRESSE OXIDATIVO, business.industry, General Neuroscience, Neurodegeneration, Autophagy, Motor Cortex, medicine.disease, Spinal cord, Rats, Oxidative Stress, 030104 developmental biology, Proteostasis, Endocrinology, medicine.anatomical_structure, Rats, Inbred Lew, Nerve Degeneration, Exercise Test, Neuron, business, 030217 neurology & neurosurgery, Oxidative stress, Motor cortex

الوصف: Proteostasis and oxidative stress were evaluated in motor cortex and spinal cord of aged Lewis rats exposed to 1 mg/kg/day of rotenone during 4 or 8 weeks, prior or after practicing three protocols of mild treadmill running. Results demonstrated that exercise done after the beginning of neurodegeneration reverted the increased oxidative stress (measured by H2O2 levels and SOD activity), increased neuron strength, and improved proteostasis in motor cortex. Spinal cord was not affected. Treadmill running practiced before neurodegeneration protected cortical motor neurons of the rotenone-exposed rats; but in this case, oxidative stress was not altered, whereas proteasome activity was increased and autophagy decreased. Spinal cord was not protected when exercise was practiced before neurodegeneration. Prolonged treadmill running (10 weeks) increased oxidative stress, autophagy, and proteasome activity, whereas neuron viability was decreased in motor cortex. In spinal cord, this protocol decreased oxidative stress and increased proteasome activity. Major conclusions were that treadmill running practiced before or after the beginning of neurodegeneration may protect motor cortex neurons, whereas prolonged mild running seems to be beneficial for spinal cord.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::358f5750b75a567d6c121c25aaf72c13Test
https://pubmed.ncbi.nlm.nih.gov/30276717Test