The Search for a Universal Treatment for Defined and Mixed Pathology Neurodegenerative Diseases DOI Open Access
Danton H. O’Day

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13424 - 13424

Published: Dec. 14, 2024

The predominant neurodegenerative diseases, Alzheimer’s disease, Parkinson’s dementia with Lewy Bodies, Huntington’s amyotrophic lateral sclerosis, and frontotemporal dementia, are rarely pure diseases but, instead, show a diversity of mixed pathologies. At some level, all them share combination one or more different toxic biomarker proteins: amyloid beta (Aβ), phosphorylated Tau (pTau), alpha-synuclein (αSyn), mutant huntingtin (mHtt), fused in sarcoma, superoxide dismutase 1, TAR DNA-binding protein 43. These proteins common attributes, making potentially universal simultaneous targets for therapeutic intervention. First, they form aggregates prior to taking on their final forms as contributors plaques, neurofibrillary tangles, bodies, other deposits. Second, the primary enzyme that directs aggregation is transglutaminase 2 (TGM2), brain-localized involved neurodegeneration. Third, TGM2 binds calmodulin, regulatory event can increase activity this threefold. Fourth, most pathology biomarkers (Aβ, pTau, αSyn, nHtt) also bind which affect ability aggregate. This review examines potential routes opened up by knowledge. end goal reveals multiple opportunities immediately available treatment devastating facing humankind.

Language: Английский

The calmodulin hypothesis of neurodegenerative diseases: searching for a common cure DOI
Danton H. O’Day

Neurodegenerative Disease Management, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 3

Published: April 2, 2025

Language: Английский

Citations

0
Calcium and Non-Penetrating Traumatic Brain Injury: A Proposal for the Implementation of an Early Therapeutic Treatment for Initial Head Insults DOI Creative Commons
Danton H. O’Day

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 853 - 853

Published: July 15, 2024

Finding an effective treatment for traumatic brain injury is challenging multiple reasons. There are innumerable different causes and resulting levels of damage both penetrating non-penetrating each which shows diverse pathophysiological progressions. More concerning that disease progression can take decades before neurological symptoms become obvious. Currently, the primary mild injury, also called concussion, bed rest despite fact majority emergency room visits due to this form. Furthermore, one-third cases progress long-term serious symptoms. This argues earliest therapeutic intervention all focus review. Calcium greatly increased in damaged regions as a result initial impact tissue well disrupted ion channels. The dysregulated calcium level feedback diversity ways further augment neurotoxicity. suggests targeting function would be strong approach. An calcium-based therapy could best developed through programs organized professional team sports where events common, large numbers subjects involved personnel available oversee documentation. review concludes with proposal focus.

Language: Английский

Citations

1
Convergence between brain aging and Alzheimer’s disease: focus on mitochondria DOI
Salvatore Vaiasicca, Marta Balietti,

Lisa Bevilacqua

et al.

Mechanisms of Ageing and Development, Journal Year: 2024, Volume and Issue: unknown, P. 112001 - 112001

Published: Oct. 1, 2024

Language: Английский

Citations

1
Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons DOI Creative Commons
Rafael Rivas‐Santisteban, Ana Muñoz, Jaume Lillo

et al.

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Nov. 15, 2024

Calcium ion (Ca2+) homeostasis is crucial for neuron function and neurotransmission. This study focused on the actions mediated by CB1 receptor (CB1R), most abundant G protein-coupled (GPCR) in central nervous system (CNS) neurons, over AT1R, which one of few CNS receptors able to regulate cytoplasmic Ca2+ levels. A functional interaction suggesting a direct association between these was detected. AT1-CB1 heteromers (AT1CB1Hets) were identified HEK-293T cells bioluminescence resonance energy transfer (BRET2). Functional interactions within complex their potential relevance Parkinson's disease (PD) assessed. In situ proximity ligation assays (PLA) AT1CB1Hets an important finding that level increase upon AT1R activation reduced presence cannabinoids acting CB1Rs. AT1CB1Het expression quantified samples from 6-hydroxydopamine (6-OHDA) hemilesioned rat model PD lower observed striatal neurons lesioned animals (versus non-lesioned). changed depending both lesion consequences levodopa administration, i.e., dyskinesias versus lack involuntary movements. partial recovery detected developed levodopa-induced dyskinesias. These findings support existence compensatory mechanism modulates susceptibility PD. Therefore, may be useful reducing calcium dyshomeostasis dyskinesia.

Language: Английский

Citations

1
Ca2+/calmodulin signaling in organismal aging and cellular senescence: Impact on human diseases DOI
Martin W. Berchtold, Antonio Villalobo

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: unknown, P. 167583 - 167583

Published: Nov. 1, 2024

Language: Английский

Citations

1
The Search for a Universal Treatment for Defined and Mixed Pathology Neurodegenerative Diseases DOI Open Access
Danton H. O’Day

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13424 - 13424

Published: Dec. 14, 2024

The predominant neurodegenerative diseases, Alzheimer’s disease, Parkinson’s dementia with Lewy Bodies, Huntington’s amyotrophic lateral sclerosis, and frontotemporal dementia, are rarely pure diseases but, instead, show a diversity of mixed pathologies. At some level, all them share combination one or more different toxic biomarker proteins: amyloid beta (Aβ), phosphorylated Tau (pTau), alpha-synuclein (αSyn), mutant huntingtin (mHtt), fused in sarcoma, superoxide dismutase 1, TAR DNA-binding protein 43. These proteins common attributes, making potentially universal simultaneous targets for therapeutic intervention. First, they form aggregates prior to taking on their final forms as contributors plaques, neurofibrillary tangles, bodies, other deposits. Second, the primary enzyme that directs aggregation is transglutaminase 2 (TGM2), brain-localized involved neurodegeneration. Third, TGM2 binds calmodulin, regulatory event can increase activity this threefold. Fourth, most pathology biomarkers (Aβ, pTau, αSyn, nHtt) also bind which affect ability aggregate. This review examines potential routes opened up by knowledge. end goal reveals multiple opportunities immediately available treatment devastating facing humankind.

Language: Английский

Citations

1