Photobiomodulation for Neurodegenerative Diseases: A Scoping Review.

Neurodegenerative diseases involve the progressive dysfunction and loss of neurons in the central nervous system and thus present a significant challenge due to the absence of effective therapies for halting or reversing their progression. Based on the characteristics of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), which have prolonged incubation periods and protracted courses, exploring non-invasive physical therapy methods is essential for alleviating such diseases and ensuring that patients have an improved quality of life. Photobiomodulation (PBM) uses red and infrared light for therapeutic benefits and functions by stimulating, healing, regenerating, and protecting organizations at risk of injury, degradation, or death. Over the last two decades, PBM has gained widespread recognition as a non-invasive physical therapy method, showing efficacy in pain relief, anti-inflammatory responses, and tissue regeneration. Its application has expanded into the fields of neurology and psychiatry, where extensive research has been conducted. This paper presents a review and evaluation of studies investigating PBM in neurodegenerative diseases, with a specific emphasis on recent applications in AD and PD treatment for both animal and human subjects. Molecular mechanisms related to neuron damage and cognitive impairment are scrutinized, offering valuable insights into PBM's potential as a non-invasive therapeutic strategy.

The Molecular Mechanisms of Action of Photobiomodulation Against Neurodegenerative Diseases: A Systematic Review.

Neurodegenerative diseases might be slow but relentless, as we continue to fail in treating or delaying their progression. Given the complexity in the pathogenesis of these diseases, a broad-acting approach like photobiomodulation can prove promising. Photobiomodulation (PBM) uses red and infrared light for therapeutic benefits, working by stimulating growth and proliferation. The implications of photobiomodulation have been studied in several neurodegenerative disease models. It has been shown to improve cell survival, decrease apoptosis, alleviate oxidative stress, suppress inflammation, and rescue mitochondrial function. In in vivo models, it has reportedly preserved motor and cognitive skills. Beyond mitochondrial stimulation, the molecular mechanisms by which photobiomodulation protects against neurodegeneration have not been very well studied. This review has systematically been undertaken to study the effects of photobiomodulation at a molecular level and identify the different biochemical pathways and molecular changes in the process. The data showed the involvement of pathways like extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), and protein kinase B (Akt). In addition, the expression of several genes and proteins playing different roles in the disease mechanisms was found to be influenced by PBM, such as neurotrophic factors and secretases. Studying the literature indicated that PBM can be translated to a potential therapeutic tool, acting through a spectrum of mechanisms that work together to decelerate disease progression in the organism, which is difficult to achieve through pharmacological interventions.

Perspective on Broad-Acting Clinical Physiological Effects of Photobiomodulation.

Research into photobiomodulation reveals beneficial effects of light therapy for a rapidly expanding list of medical conditions and illnesses. Although it has become more widely accepted by the mainstream medicine, the effects and mechanisms of action appear to be poorly understood. The therapeutic benefits of photobiomodulation using low-energy red lasers extend far beyond superficial applications, with a well-described physics allowing an understanding of how red lasers of certain optimum intensities may cross the cranium. We now have a model for explaining potential therapeusis for applications in functional neurology that include stroke, traumatic brain injury, and neurodegenerative conditions in addition to the currently approved functions in lipolysis, in onychomycosis treatment, and in pain management.

A comprehensive review on therapeutic potentials of photobiomodulation for neurodegenerative disorders.

A series of experimental trials over the past two centuries has put forth Photobiomodulation (PBM) as a treatment modality that utilizes colored lights for various conditions. While in its cradle, PBM was used for treating simple conditions such as burns and wounds, advancements in recent years have extended the use of PBM for treating complex neurodegenerative diseases (NDDs). PBM has exhibited the potential to curb several symptoms and signs associated with NDDs. While several of the currently used therapeutics cause adverse side effects alongside being highly invasive, PBM on the contrary, seems to be broad-acting, less toxic, and non-invasive. Despite being projected as an ideal therapeutic for NDDs, PBM still isn't considered a mainstream treatment modality due to some of the challenges and knowledge gaps associated with it. Here, we review the advantages of PBM summarized above with an emphasis on the common mechanisms that underlie major NDDs and how PBM helps tackle them. We also discuss important questions such as whether PBM should be considered a mainstay treatment modality for these conditions and if PBM's properties can be harnessed to develop prophylactic therapies for high-risk individuals and also highlight important animal studies that underscore the importance of PBM and the challenges associated with it. Overall, this review is intended to bring the major advances made in the field to the spotlight alongside addressing the practicalities and caveats to develop PBM as a major therapeutic for NDDs.

Low-Dose Radiation Therapy for Neurological Disorders: A Double-Edged Sword.

Radiation therapy targeting the central nervous system is widely utilized for the management of various brain tumors, significantly prolonging patient survival. Presently, investigations are assessing both clinical and preclinical applications of low-dose radiation (LDR) for the treatment of neuropathological conditions beyond tumor therapy. Special focus is given to refractory neurodegenerative diseases linked to neuroinflammation, such as Alzheimer's and Parkinson's diseases, where LDR has shown promising results. This comprehensive review examines the existing experimental data regarding the utilization of LDR in neurological disorders. It covers potential advantages in reducing neurodegenerative alterations and inflammation, as well as possible adverse effects, including neurological impairments. The review underscores the importance of the exposure protocol and the age at which LDR is administered in the context of the nervous system's pathological and physiological states, as these elements are crucial in determining LDR's therapeutic and toxic outcomes. The article concludes with a discussion on the future directions and challenges in optimizing LDR use, aiming to reduce toxicity while effectively managing neurological disorders.

A systematic review of the effect of photobiomodulation on the neuroinflammatory response in animal models of neurodegenerative diseases.

This systematic review examines the effect of photobiomodulation (PBM), the application of red to near infrared light on body tissues, on the neuroinflammatory response and oxidative stress in animal models of neurodegenerative diseases. The research question and search protocol were prospectively registered on the PROSPERO database. Neurodegenerative diseases are becoming ever more prevalent in the ageing populations across the Western world, with no disease-modifying or neuroprotective treatment options being available. Hence there is a real need for the development of effective treatment options for patients. Inflammatory responses and oxidative stress within the central nervous system have a strong correlation with neuronal cell death. PBM is a non-invasive therapeutic option that has shown efficacy and promising effects in animal models of neurodegenerative disease; many studies have reported neuroprotection and improved behavioural outcomes. To the best of our knowledge, there has been no previous study that has reviewed the anti-inflammatory and the antioxidant effect of PBM in the context of neurodegeneration. This review has examined this relationship in animal models of a range of neurodegenerative diseases. We found that PBM can effectively reduce glial activation, pro-inflammatory cytokine expression and oxidative stress, whilst increasing anti-inflammatory glial responses and cytokines, and antioxidant capacity. These positive outcomes accompanied the neuroprotection evident after PBM treatment. Our review provides further indication that PBM can be developed into an effective non-pharmacological intervention for neurodegenerative diseases.

Control of Neuroinflammation through Radiation-Induced Microglial Changes.

Microglia, the innate immune cells of the central nervous system, play a pivotal role in the modulation of neuroinflammation. Neuroinflammation has been implicated in many diseases of the CNS, including Alzheimer's disease and Parkinson's disease. It is well documented that microglial activation, initiated by a variety of stressors, can trigger a potentially destructive neuroinflammatory response via the release of pro-inflammatory molecules, and reactive oxygen and nitrogen species. However, the potential anti-inflammatory and neuroprotective effects that microglia are also thought to exhibit have been under-investigated. The application of ionising radiation at different doses and dose schedules may reveal novel methods for the control of microglial response to stressors, potentially highlighting avenues for treatment of neuroinflammation associated CNS disorders, such as Alzheimer's disease and Parkinson's disease. There remains a need to characterise the response of microglia to radiation, particularly low dose ionising radiation.

Photostimulation of mitochondria as a treatment for retinal neurodegeneration.

Absorption of photon energy by neuronal mitochondria leads to numerous downstream neuroprotective effects. Red and near infrared (NIR) light are associated with significantly less safety concerns than light of shorter wavelengths and they are therefore, the optimal choice for irradiating the retina. Potent neuroprotective effects have been demonstrated in various models of retinal damage, by red/NIR light, with limited data from human studies showing its ability to improve visual function. Improved neuronal mitochondrial function, increased blood flow to neural tissue, upregulation of cell survival mediators and restoration of normal microglial function have all been proposed as potential underlying mechanisms of red/NIR light.

Low-Level Laser Therapy to the Bone Marrow Ameliorates Neurodegenerative Disease Progression in a Mouse Model of Alzheimer's Disease: A Minireview.

OBJECTIVE: This communication reviews the ability of low-level laser therapy (LLLT) to stimulate mesenchymal stem cells (MSCs) in autologous bone marrow (BM) to enhance the capacity of MSCs to infiltrate the brain, clear ß-amyloid, and improve cognition. BACKGROUND: We recently reported that LLLT applied to the BM enhanced the proliferation of MSCs and their mobilization toward the ischemic heart region, suggesting a possible application of this approach in regenerative medicine and neurodegenerative diseases. It was also shown that circulating monocytes can infiltrate the brain and reduce brain amyloid load in an Alzheimer's disease (AD) mouse model. METHODS AND RESULTS: MSCs from wild-type mice stimulated with LLLT demonstrated an increased ability to maturate toward a monocyte lineage and to increase phagocytosis of soluble Aß in vitro. Furthermore, weekly LLLT for 2 months to the BM, starting at 4 months of age (progressive stage of the disease in these 5XFAD transgenic male mice), improved memory and spatial learning, compared to a sham-treated AD mouse model. Histology revealed a significant reduction in Aß brain burden in the laser-treated mice compared to the nonlaser-treated ones. CONCLUSIONS: The application of LLLT to the BM is suggested as a therapeutic approach in progressive stages of AD, and its potential role in mediating MSC therapy in brain amyloidogenic disease is implied.

Neurological and psychological applications of transcranial lasers and LEDs.

Transcranial brain stimulation with low-level light/laser therapy (LLLT) is the use of directional low-power and high-fluency monochromatic or quasimonochromatic light from lasers or LEDs in the red-to-near-infrared wavelengths to modulate a neurobiological function or induce a neurotherapeutic effect in a nondestructive and non-thermal manner. The mechanism of action of LLLT is based on photon energy absorption by cytochrome oxidase, the terminal enzyme in the mitochondrial respiratory chain. Cytochrome oxidase has a key role in neuronal physiology, as it serves as an interface between oxidative energy metabolism and cell survival signaling pathways. Cytochrome oxidase is an ideal target for cognitive enhancement, as its expression reflects the changes in metabolic capacity underlying higher-order brain functions. This review provides an update on new findings on the neurotherapeutic applications of LLLT. The photochemical mechanisms supporting its cognitive-enhancing and brain-stimulatory effects in animal models and humans are discussed. LLLT is a potential non-invasive treatment for cognitive impairment and other deficits associated with chronic neurological conditions, such as large vessel and lacunar hypoperfusion or neurodegeneration. Brain photobiomodulation with LLLT is paralleled by pharmacological effects of low-dose USP methylene blue, a non-photic electron donor with the ability to stimulate cytochrome oxidase activity, redox and free radical processes. Both interventions provide neuroprotection and cognitive enhancement by facilitating mitochondrial respiration, with hormetic dose-response effects and brain region activational specificity. This evidence supports enhancement of mitochondrial respiratory function as a generalizable therapeutic principle relevant to highly adaptable systems that are exquisitely sensitive to energy availability such as the nervous system.

Cysteamine: an old drug with new potential.

Cysteamine is an amino thiol with the chemical formula HSCH2CH2NH2. Endogenously, cysteamine is derived from coenzyme A degradation, although its plasma concentrations are low. Most experience with cysteamine as a drug originates from the field of the orphan disease cystinosis, in which cysteamine is prescribed to decrease intralysosomal cystine accumulation. However, over the years, the drug has been used for several other applications both in vitro and in vivo. In this article, we review the different applications of cysteamine, ending with an overview of ongoing clinical trials for new indications, such as neurodegenerative disorders and nonalcoholic fatty liver disease (NAFLD). The recent development of an enteric-coated cysteamine formulation makes cysteamine more patient friendly and will extend its applicability for both old and new indications.

Radiation therapy for nonmalignant diseases in Germany. Current concepts and future perspectives.

BACKGROUND: Radiotherapy (RT) of nonmalignant diseases has a long-standing tradition in Germany. Over the past decade significant theoretical and clinical progress has been made in this field to be internationally recognized as an important segment of clinical RT. This development is reflected in a national patterns-of-care study (PCS) conducted during the years 2001-2002. MATERIAL AND METHODS: In 2001 and 2002, a questionnaire was mailed to all RT facilities in Germany to assess equipment, patient accrual, RT indications, and treatment concepts. 146 of 180 institutions (81%) returned all requested data: 23 university hospitals (UNI), 95 community hospitals (COM), and 28 private institutions (PRIV). The specific diseases treated at each institution and the RT concepts were analyzed for frequencies and ratios between the different institution types. All data were compared to the first PCS in 1994-1996. RESULTS: In 137 institutions (94%) 415 megavoltage units (mean 1.7; range 1-4), and in 78 institutions (53%) 112 orthovoltage units (mean 1.1; range 0-2) were available. A mean of 37,410 patients were treated per year in all institutions: 503 (1.3%) for inflammatory disorders, 23,752 (63.5%) for degenerative, 1,252 (3.3%) for hypertrophic, and 11,051 (29.5%) for functional, other and unspecified disorders. In comparison to the first PCS there was a significant increase of patients per year (from 20,082 to 37,410; +86.3%) in most nonmalignant diseases during the past 7-8 years. Most disorders were treated in accordance with the national consensus guidelines: the prescribed dose concepts (single and total doses) varied much less during the period 2001-2002 in comparison with the previous PCS in 1994-1996. Only five institutions (3.4%) received recommendations to change single or total doses and/or treatment delivery. Univariate analysis detected significant institutional differences in the use of RT for various disorders. CONCLUSION: RT is increasingly accepted in Germany as a reasonable treatment option for many nonmalignant diseases. The long-term perspective and research plan will have to include various updates of PCS, re-writing of consensus guidelines, introduction of registries for rare nonmalignant disorders, and clinical controlled studies even for so-called established indications, as international acceptance is based on the criteria of evidence-based medicine.