Neurodegeneration is complex. Alzheimers has become an umbrella term and is the prima donna for research. The fundamental belief based on protein caused pathology for AD seems to have been a goose chase. What if they have overlooked something?
I have come to the simple layman’s view that mitochondria is life in the most simplistic way. What factors are eluding researchers?
Infrared light photons excite mitochondria. Infrared technology is used in motion detection in any office building you go into, in night vision enhancement equipment, etc.
We are infrared emitting biological structures. I can’t help but think that should factor into our wellness strategies.
-Rainey
I’ll be damned!
The clues.
Another clue.
An organic, curable cause for what had brought so much trauma, stigma and heartache in mom’s life provided answers for mom. Not the most accurate answers, but the cure was real for her family and others she knew at that time. This activism was during a time of growing awareness of the systemic injustices in our nation’s mental health institutions . One Flew Over the Cuckoo’s Nest was released in 1975. Mom later edited out the phrase schizophrenia once she learned more, but that she self identified with the illness is undeniable. Her credulity, again, seems an indicator of neurodivergence.
Another clue.
Seems like a description of the ocular migraines mom told me she suffered from.
“Use me to help stop suffering and pain.”
I am looking for the key to my mom’s long complicated medical history.
I don’t know if I can succinctly give voice to the saga of a child born in 1935 into a household under the shadow of what was considered mental illness. From my deep dive into mom’s own manuscripts as a poet and short story writer and my layperson’s attempt of forensic level examination of her medical record, I believe we may have maternal inheritance mitochondrial dysfunction. This belief has trickled from diagnosis of my grandchildren with autism, developmental delay, and ADHD, up to my daughters with ADHD and immune compromised health, to me with autistic like special interests and hyperfocus. My mom, alternately called a crazy woman, hypochondriac, or schizophrenic, now has an egregious misdiagnosis of bipolar with acute mania and psychosis. Her struggles seem textbook autism for women. The writing has been on the wall, generation after generation, it just takes translating into a non-medical dialect. I am fighting for her rights as she experiences one adverse effect to psychoactive medications after another. The neurological effects are hastening her passage out of this realm.
In mom’s childhood eugenics tainted the community around her. Upon occasion adults in her own family openly declared as she was listening that she was a tragic waste of money and resources and should have been left to die so that the other children would have more. A morbid curiosity in the town people about a sick child and absolute ignorance made clinic visits for treatment of erysipelas (probably presented as a flesh eating disease) a gauntlet of humiliation. Spectators stopped on the sidewalks and in the middle of the street to get a glimpse of the little girl getting twice daily injections to treat life threatening “syphilis.”
My heart is rent knowing this new understanding is too little, too late for it to make much difference in mom’s life. She is losing neural control of her body, a once gifted mind trapped in a bone and flesh cage, her spirit dims noticeably week to week. But this knowledge will help my children and their children. Mom’s motto was always for her life struggles be used to help others. But the story has to be told, an audience has to be reached…
I am building this website for her as a memorial of the incredible resilience she has displayed and to shed light upon the struggle yet others, like her, now have and will continue to have finding understanding and appropriate care. Mom never had the organizational skills to make her self described purpose in life to ease other sufferings go much further than her pen put to paper. But she found so many answers, just did not cobble them together or have the focus to make a coherent narrative. Maybe I can do that is some small measure.
Paywalls without a supporting “institution,” might as well be a brick wall for layperson researching illnesses….
Stressful experiences or exposures encompass a wide variety of environmental demands on the individual. A stress exposure may have the potential for positive outcomes marked by reward, such as a job interview or an exam. In such situations, the stress-related physiological response is activated and deactivated over the time course of a discrete stressor. Acute stress may also occur in the setting of a profoundly negative experience, such as the death of a parent or spouse. In the wake of such events, personal resources and external support may allow the individual to prevail and continue to thrive. In so-called “toxic stress,” the exposure may be severe or chronic, and the individual lacks either internal or external resources needed to promote resilience, resulting in the absence of control over the environment. In such circumstances, the physiological and behavioral recalibrations may serve to protect some functions while disadvantaging others. Untethered, maladaptive processes serve to promote physiological dysregulation and pathology (Shonkoff et al. 2009). Chronic, prolonged exposure to toxic stress imparts both disorders of mental and physical health (Wegman & Stetler 2009, Rich-Edwards et al. 2010, Widom et al. 2015, Basu et al. 2017, Jakubowski et al. 2018).
Naig Gueguen, Olivier Baris, Guy Lenaers, Pascal Reynier, Marco Spinazzi,
Secondary coenzyme Q deficiency in neurological disorders,
Free Radical Biology and Medicine,
Volume 165,
2021,
Pages 203-218,
ISSN 0891-5849,
https://doi.org/10.1016/j.freeradbiomed.2021.01.017.
(https://www.sciencedirect.com/science/article/pii/S0891584921000344)
Abstract: Coenzyme Q (CoQ) is a ubiquitous lipid serving essential cellular functions. It is the only component of the mitochondrial respiratory chain that can be exogenously absorbed. Here, we provide an overview of current knowledge, controversies, and open questions about CoQ intracellular and tissue distribution, in particular in brain and skeletal muscle. We discuss human neurological diseases and mouse models associated with secondary CoQ deficiency in these tissues and highlight pharmacokinetic and anatomical challenges in exogenous CoQ biodistribution, recent improvements in CoQ formulations and imaging, as well as alternative therapeutical strategies to CoQ supplementation. The last section proposes possible mechanisms underlying secondary CoQ deficiency in human diseases with emphasis on neurological and neuromuscular disorders.
Keywords: Coenzyme Q; Mitochondria; Neurological diseases; Secondary coenzyme Q deficiency; Brain; Muscle
Although CoQ10 supplementation is an obvious and appealing therapeutic strategy for patients with MSA, CoQ10 and its derivatives have failed to show efficacy in several neurologic disorders, including Parkinson disease and Friedreich ataxia.14,15 In these disorders, mitochondrial functions are compromised; however, there is no evidence of CoQ10 deficiency, since levels of CoQ10 are normal in the brains of patients with Parkinson disease10,11 and in the cerebellum of patients with Friedreich ataxia.10 Mitochondria are responsible for many important biological functions; therefore, CoQ10 might not be able to rescue mitochondrial defects specific to Parkinson disease or Friedreich ataxia. On the other hand, the genetic evidence along with results of postmortem brain examinations and studies of peripheral blood biomarkers consistently indicate that CoQ10 might play a major role in MSA. Another possible cause for the lack of response to CoQ10 supplementation in Parkinson disease and Friedreich ataxia may be the low absorption and bioavailability that limit the increase of CoQ10 in cell mitochondria, where it is biologically active.9 This limitation is even more prominent in the brain because the exogenous CoQ10must be able to cross the blood-brain barrier to effectively treat neurologic disorders; therefore, large doses of CoQ10 (approximately 1200-2400 mg/d) are generally needed to reach the brain.14,15 From the previous experience of clinical trials of CoQ10,14 these doses are generally well-tolerated. Moreover, efficacy of the therapy may be increased by the use of ubiquinol, the reduced form of CoQ10, which has greater bioavailability than CoQ10. Accordingly, a Japanese consortium led by Shoji Tsuji, MD, PhD, has initiated a safety and pharmacokinetic study on a reduced form of CoQ10 (MSA-01) in healthy individuals. The goal of the study is to investigate the CoQ10 concentration in plasma, leukocytes, and cerebrospinal fluid with different doses of MSA-01. Once the optimal dose has been determined, a randomized, double-blind, placebo-controlled clinical trial for MSA will soon be under way and plasma CoQ10 levels might serve as a biomarker to assess target engagement.
In conclusion, the recent discoveries of COQ2 mutations in rare patients with MSA and of CoQ10 deficiency in the brain and blood of patients with MSA may lead to mechanism-based and rationale therapies for MSA, a rapidly progressive disorder in need of a disease-modifying therapy.
Stress and Psychiatric Disorders: The Role of Mitochondria.
Stressful experiences or exposures encompass a wide variety of environmental demands on the individual. A stress exposure may have the potential for positive outcomes marked by reward, such as a job interview or an exam. In such situations, the stress-related physiological response is activated and deactivated over the time course of a discrete stressor. Acute stress may also occur in the setting of a profoundly negative experience, such as the death of a parent or spouse. In the wake of such events, personal resources and external support may allow the individual to prevail and continue to thrive. In so-called “toxic stress,” the exposure may be severe or chronic, and the individual lacks either internal or external resources needed to promote resilience, resulting in the absence of control over the environment. In such circumstances, the physiological and behavioral recalibrations may serve to protect some functions while disadvantaging others. Untethered, maladaptive processes serve to promote physiological dysregulation and pathology (Shonkoff et al. 2009). Chronic, prolonged exposure to toxic stress imparts both disorders of mental and physical health (Wegman & Stetler 2009, Rich-Edwards et al. 2010, Widom et al. 2015, Basu et al. 2017, Jakubowski et al. 2018).
Daniels TE, Olsen EM, Tyrka AR. Stress and Psychiatric Disorders: The Role of Mitochondria. Annu Rev Clin Psychol. 2020 May 7;16:165-186. doi: 10.1146/annurev-clinpsy-082719-104030. Epub 2020 Feb 24. PMID: 32092280; PMCID: PMC8007172.
