Frontotemporal dementia and amyotrophic lateral sclerosis: Revisiting one of the first case reports with neuropathological examination

Nitrini, Ricardo

doi:10.1590/s1980-57642014dn81000013

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Microglia are activated in disease conditions, releasing proinflammatory cytokines which cause neuroinflammation and neuronal injury. Phagocytosis and autophagy are interrupted, contributing to the aggregation of proteins and mitochondrial disorders, leading to the enhanced generation of ROS that causes further inflammation [ 109 , 141 , 142 ]. While emerging proof indicates that inflammation performs a contributory role in the pathogenesis of AD, inflammatory markers have not yet been well identified as a valuable instrument for diagnosing AD.…”

Section: Future Directionsmentioning

confidence: 99%

Neuroinflammation: A Potential Risk for Dementia

Ahmad

Kareem

Khushtar

et al. 2022

IJMS

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Dementia is a neurodegenerative condition that is considered a major factor contributing to cognitive decline that reduces independent function. Pathophysiological pathways are not well defined for neurodegenerative diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in the brain contributing toward their pathology. Microglia of the central nervous system (CNS) are the principal components of the brain’s immune defence system and can detect harmful or external pathogens. When stimulated, the cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, and nitrogen species in order to preserve the cell’s microenvironment. These proinflammatory markers include cytokines such as IL-1, IL-6, and TNFα chemokines such as CCR3 and CCL2 and CCR5. Microglial cells may produce a prolonged inflammatory response that, in some circumstances, is indicated in the promotion of neurodegenerative diseases. The present review is focused on the involvement of microglial cell activation throughout neurodegenerative conditions and the link between neuroinflammatory processes and dementia.

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Section: Future Directionsmentioning

confidence: 99%

Neuroinflammation: A Potential Risk for Dementia

Ahmad

Kareem

Khushtar

et al. 2022

IJMS

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“…The second variant (c.454GTAC > G, p.ΔI153) was identified in a man with ALS onset aged 53 years who died aged 54 years. Although he had no family history of ALS, his mother developed insulin-dependent diabetes mellitus and narcolepsy, and his father presented with early onset dementia, a condition known to precede motor impairment in some people with ALS [14]. This mutation produces an inframe deletion of the isoleucine 153 located in the second transmembrane helix of Ca v 3.2, a region highly conserved across Ca v 3.2 channel orthologs ( Fig.…”

Section: Whole Genome Sequencing Identifies Heterozygous Cacn A1h Mutmentioning

confidence: 99%

A rare CACNA1H variant associated with amyotrophic lateral sclerosis causes complete loss of Cav3.2 T-type channel activity

et al. 2020

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of cortical, brain stem and spinal motor neurons that leads to muscle weakness and death. A previous study implicated CACN A1H encoding for Ca v 3.2 calcium channels as a susceptibility gene in ALS. In the present study, two heterozygous CACNA1H variants were identified by whole genome sequencing in a small cohort of ALS patients. These variants were functionally characterized using patch clamp electrophysiology, biochemistry assays, and molecular modeling. A previously unreported c.454GTAC > G variant produced an inframe deletion of a highly conserved isoleucine residue in Ca v 3.2 (p.ΔI153) and caused a complete loss-of-function of the channel, with an additional dominantnegative effect on the wild-type channel when expressed in trans. In contrast, the c.3629C > T variant caused a missense substitution of a proline with a leucine (p.P1210L) and produced a comparatively mild alteration of Ca v 3.2 channel activity. The newly identified ΔI153 variant is the first to be reported to cause a complete loss of Ca v 3.2 channel function. These findings add to the notion that loss-of-function of Ca v 3.2 channels associated with rare CACNA1H variants may be risk factors in the complex etiology of ALS.

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“…Although the primary symptoms of ALS are associated with motor dysfunction (i.e. muscle weakness, spasticity, and dysphagia), up to 50% of patients develop cognitive and/or behavioral impairment during the course of disease, and 13% of patients present with concomitant behavioral variant frontotemporal dementia (FTD) [5,6]. Anyhow, loss of respiratory muscle innervation and associated complications are the most frequent causes of death [7].…”

Section: Introductionmentioning

confidence: 99%

Emerging technologies for management of patients with amyotrophic lateral sclerosis: from telehealth to assistive robotics and neural interfaces

et al. 2022

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Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and subsequently paralysis. It begins subtly with focal weakness but spreads relentlessly to involve most muscles, thus proving to be effectively incurable. Typically, death due to respiratory paralysis occurs in 3-5 years. To date, it has been shown that the management of ALS patients is best achieved with a multidisciplinary approach, and with the help of emerging technologies ranging from multidisciplinary teleconsults (for monitoring the dysphagia, respiratory function, and nutritional status) to brain-computer interfaces and eye tracking for alternative augmentative communication, until robotics, it may increase effectiveness. The COVID-19 pandemic created a spasmodic need to accelerate the development and implementation of such technologies in clinical practice, to improve the daily lives of both ALS patients and caregivers. However, despite the remarkable strides that have been made in the field, there are still issues to be addressed. This review will be discussed on the eureka moment of emerging technologies for ALS, used as a blueprint not only for neurodegenerative diseases, examining the current technologies already in place or being evaluated, highlighting the pros and cons for future clinical applications.

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Frontotemporal dementia and amyotrophic lateral sclerosis: Revisiting one of the first case reports with neuropathological examination

Cited by 4 publications

References 21 publications

Neuroinflammation: A Potential Risk for Dementia

Neuroinflammation: A Potential Risk for Dementia

A rare CACNA1H variant associated with amyotrophic lateral sclerosis causes complete loss of Cav3.2 T-type channel activity

Emerging technologies for management of patients with amyotrophic lateral sclerosis: from telehealth to assistive robotics and neural interfaces

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